most fluid are intracellular isoosmotic conc. Na+/K+ ATPase depends on: -Na conc inside -K+ outside -Energy supply(ATP) -Temprature -Inhibitors? Ouabain RM potential -70mV for majority of neurons Threshold potential -55mV Equilibrium potential hypothetical potential difference across cell membrane at which net cross of ions due to gradients would be equal to 0 Sensory neuron -graded potentials -myelinated/unmyelinated axons Chapter 8 - APs, GPs etc. Axon - transmits electrical impulse to distal end where electrical signal -> chemical via: Neirotransmitter, neuromodulator,(neurohormone) -Axons lack RER and ribosomes hence all proteins are synthesized in soma for axonal transport Slow and fast axonal transport Glial cells - support for neurons PNS: Schwann cells - myelination (1 node 1 Sch cell) Satellite cells - ganglions CNS: Oligodendrocytes - myelination (several nodes) Microglial cells - immune response Astrocytes - blood brain barrier Ependymocytes - neura stem cells + compartments Nerve and muscle cells are excitable tissues Vm - resting membrane potential -Uneven distribution of ions across the membrane -Mainly due to K+ -90mV or - 70mV in resting neuron Na+ in depolarize - too much K+ out hyperpolarize(become more negative) Hypopolarize(become more +/ närmare 0 / more excitable) 1. Mechanically gated ion channels -In sensory neurons open to physical forces like pressure or stretch 2.Chemically gated ion channels Respond to ligands(neurotransmitters/neuromodulators) & intracellular signal molecules. 3.Voltage gates ion channels -Resoond to change in resting membrane potential - depends on threshold —>Depolarization opens fast gated Na+ channels and then K+ channels This can work as a swing door - swings back closed when electrical signal passed It can also be inactivated - works like an automatic timed door (off button) Net flow of ions depend on electrochemical gradient Graded potentials -Variable in strength -Loose strength on the way (stone in water) -If the stone is big then more likely to fire AP -> amplitude is directly proportional to strength of triggering event -Occurs in cells body(soma) -Loose strength due to K+leak and cytoplasmic resistance Action potential -Large depolarizations -Do not loose strength -Rapid signalling over long distances -Works like a domino -Peaks at + 30mV -Equilibrium for Na+ at +60mv? -Falling phase: increase of K+ leak - inc negativity and fall of AP -SPeed depends on diameter and ions leakage - large and myelinated -> fastest conduction Graded Potential Action potential Input signal Conducting signal In cell body trigger zone->axon Mechanical Chemical or voltage G voltage gated Na+ K+ Cl- ions Na+ and K+ Depolarizing Hyperpolarizing Depolarizing Summation All or none Gated channels NO threshold threshold -> open ion chan no minimum for initiation threshold -55mV needed no refractory period refractory period strength by frequency No AP in refractiory period Na+ channels has two gates Activation gate and deactivation gate -55mV - Activation gate opens 0mV - Na+ enters +30mV - inactivation gate closes (peak of curve) Repolarization - activation gate closes and inactivation gate open - reset to original state Absolute refractory period Na+ channels must reset to original position (1-2 millisek) -> AP cannot fire now and no moving backward The relative refractory period - Larger than normal stimulus can trigger AP At depolarization site of axon + inside -outside Nomal: - inside ++outside Nodes of ranvier has high concentration of Na+ channels -> Saltatory conduction, like jumping In demyelinating diseases like MS - conduction is slowed Chemical factors -Neurotoxins blocking Na+ channels, neurotoxins fails to pass signal to postsynaptic neuron -Botulin? -Snake poison? Normal K+ conc = 3.5-5mmol/L Hypokalemia -Increased electronegativity -Farther away from threshold -Presents as muscle weakness Hyperkalemia -Decreased electronegativity (more + cell) - K+ will not leak out as fast(osmos) -Hypersensitive neurons -Fire AP to smaller GP Hypernatremia - hypersensitive neurons Hyponatremia - muscle cramps Electrical synapses -Mainly in CNS -Smooth m. -Gapjunctions allow chemical signaling molecules to pass electrically Chemical synapses -Electrical signal becomes a chemical neurocrine -Neurotransmitter - rapid and local in one synapse -Neuromodulator - can be synaptic and non synaptic, slower acting. Auto/paracrine Neurohormones bind to ionotropic receptors or metabotropic(G-protein coupled) Circulate in blood Neurotransmitters Released from vesicles on demand by exocyotosis into synaptic cleft Botulin and other toxins block this exocytosis apparatus Glutamate - main excitatory in CNS, act on ionotropic and metabotropic receptors. aspartate is another one excitatory GABA - Main inhibitory in brain made from glycine Glycine - main inhibitory in spinal cord - Cl- channels for hyperpolarization Supstance P - pain pathways and pain relier(opiods) ATP/AMP - Can act as Nts, purines. In CNS and heart Nitric Oxide - Acetylcholine- Epinephrine- Norepinephrine- Depolarization leads to Ca2+ influx along gradient -> binds to proteins triggering exocytosis -> Nt released into synaptic cleft Then vesicles are endocytosed and retrogaededly transported back. AcH becomes Acetyl + choline by Acetylcholine esterase MAO breaks down norepi in mitochondria -Ability for neurons to change activity at synapses - synaptic plasticity 2nd msg metabotrppic by neuromodulators Fast ion channels by neurotransmitters Cell response of postsynaptic neuron determined by summed input from presynaptic neuron EPSP - excitatory depolarization Na+ or Ca2+ inflow IPSP - inhibitory hyperpolarization - Cl- inflow or K+ outflow Suprathreshold - EPSP> IPSP -> AP At postsynaptic cell Spatial summation: graded potentials arrive at different regions, summed E.g inhibition - 3x convergence: 2x EPSP + 1x IPSP -> subthreshold sum ! Inhibition does not always require multiple neurons - if IPSP/EPSP arrive close in time they can be summed Temporal summation - GPs close in time Spatial + temporal summation = postsynaptic integration Presynaptic inhibition -Inhibitory neursons decrease amount of neurotransmitter release(depolarization) -hyperpolarization More precise than postsynaptic inhibition -> Target response change This is all done by neuromodulators -> no response or weaker response in target cell A Upon injury to a neuron -proximal stump regenerates by support of glial cells -distal stump macrophaged Factors effecting nerve conduction -pressure - tingling, CP ulnar nerve -decreased temp -> reduced pain. if ice crystals in cell, irreversible -toxins -etherethyl ethanol - destroy lipid bilayer, on lab, irreversible Chapter 6 - Communication Local communication Gap junctions -Cytoplasmic bridges between adjacent cells -2x connexins -> connexons(protein channel) that opens/closes -For small ions and molecules:ATP amino acids -The only mean by which electrical signals pass directly from cell->cell Contact dependent signals Surface molecule of one cell ->membrane protein of another cell In nerve development and immune system Paracrine: Cells in vicinity. Histamine acts this way Autocrine - cell act upon self Long distance - Endocrine system Chemical - hormones in blood In contact with all cells - the ones with correct receptors mediate a response Cytokines Local and long distance Synthesized in response to stimuli Act broader than hormones, produced by all cells, made on demand A cell can respond to the signal if it has appropriate receptor Ligand->receptor->activation->intracellular activation ->synthesis of target proteins->response RECEPTORS Lipophilic - signalling molecules can diffuse through membrane and bind to nucleus/cytosol membrane. Common in gene activation. Usually hormones Lipophobic - Ligand need receptor protein in membrane. -> Rapid response -Ligand gated channel -Gprotein coupled receptor - a transducer - activates 2nd msg system -Receptor enzyme -Intergrins G-protein coupled receptors -Pass 7x across membrane -Inactive G-protein bound to GDP -GDP->GTP activates Gprotein ligand binds->phospohorylating->activation -Amplifyers: adenyl cyclase and phospholipase C Lipophobic G-protein - cAMP Adenyl cyclase converts ATP-> cAMP cAMP activates protein kinase A - PKA ->phosphorylation and signal cascade Lipid derived G-protein - phospholipase C Phospholipase c converts a membrane phospholipid into Diaglycerol - activates PKC IP3 - Leaves membrane, RyR Ca2+ channel on ER -> C2+ release in cytosol Integrins Anchored to cytoskeleton Important in blood clotting Ligand gated channels Fastest Ion channels along gradients Orphan receptors - no known ligand- Eicasoid signal molecules from archidonic acid Leukotriennes?? SIGNALING MOLECULES/LIGANDS Calcium -Voltage/Ligand/Mechanically gated Ca2+ channels -Released intracellularly by IP3 -Stored in ER -Ca2+ to calmodulin - enzyme activity in smooth m. -Ca2+ to troponin -> m. contraction -Ca2+ to channels altering their state (Ca2+ activated K+ channel) NO - dilates bloodvessels. cGMP formation. Neurotransmitter in brain CO-toxic H2S - relaxes bloodvessels in cardiovascular system Usually cell response depends on receptor not on ligand Ligand -> response A in tissue X response B in tissue Y This is explained by ligands binding to different isoforms - e.g adenergic receptors. Epinephrine to alpha receptors - vessel constriction Epinephrine to Beta receptors - vessel dilation Also different ligand can bind to same receptor norepi/epi in fight/flight respond can bind to both alpha and beta receptors Antagonist - ligand that occupy/block Agonist - ligand that activate Down regulation - decrease in receptor on surface by endocytosis. Too much agonists e.g. Can also be done by desensitization (phosphorylation of B receptor) Drug tolerance can partly be explained by down regulation - not as effective response to high ligand concentration. Up regulation - Less internalization, hypersensitive receptors. Response to too low ligand concentration Homeostatic reflex pathways -Some systems are under tonic control - signal always present, volume up/down -Systems not under tonic control are under antagonistic control - e.g autonomic control of HR -Chemical signals having opposing effects - antagonistic -An antagonistic signal in one tissue may be cooperative in other Sphincters are under tonic control Other smooth m.-undre antagonistic control Reflex control pathway Stimilus->sensor/receptor->input signal -> integrating center -> output signal ->target -> response Stimilus - change of variable (02, BP) ->sensor/receptor - constantly monitors environment of variable ->input signal - sensor sensed change, sends a signal to reflex integrating center -> integrating center - compares input with set point -> output signal - initiated if variable changed out of range. sends efferent chemical/elecrtical signal to ->target - effector cell that carries out appropriate -> response ! Sensory receptors respond to changes in environment not the same as protein receptors Central receptors - brain, eye, ear , nose Peripheral receptors - in skin, internal organs etc All sensors has a threshold, if stimuli is below - no response Integrating center in endocrine reflexes - the endocrine cell itself In CNS - brain and spinal cord If there is a single stimulus IC has a simple task Usually multiple - IC sorts out what is most important’ Output is always electrical and chemical by efferent neuron in neural reflexes Secreted in blood by endocrine R The cellular response might be different from systemic response to reflex E.g vasodilation of cells causes systemic response of increased bloodflow Neural reflex Endocrine reflex Specifity 1x neuron specific target Lot of exposed cells, need specific receptor Nature elecrical & chemical chemical into blood Speed rapid slower Duration of AP short can be longer with neuromodulators longer response Coding for identical signal intensity:frequency of signal intensity:amount of hormone secretes These 2 reflex systems better viewed as a combo not two separate systems Complex reflex control centers has more than one integrating center Simple endocrine pathway Endocrine cell is both censor and IC ->hormone release No input needed- Target is any cell with appropriate receptor E.g insulin secretion SImple neuronal reflex - knee jerk Neurohormone reflex - identical to neural except neurohormone travel in blood E.g breastmilk - oxytocin reflex Autonomic nervous system PNS efferent division Somatic motor neurons - skeletal m. control Autonomic neurons - smooth m., cardiac m., glands, adipose tissue Autonomic division -involuntary and self governing -two efferent neurons CNS->GGL GGL->TISSUE -Divergence! 1 preggl neuron synapse with 8-9 post -> 1 CNS signal effect a lot of target cells simultaneously -Cell bodies in lateral horn on spinal cord Peripheral ganglions has neurons as small integrated centers technically a reflex could be integrated here Antagonistic control - hallmark for ANS ! Exceptions are sweat glands, smooth m. of blood vessels and sphincters - sympathetic tonic control Sympathetic division - fight/flight -T1-L2 -Sphlancninc nn. -Use acetylchole(nicotinic) pre & norepinephrine(adenergic) post -Paravertebral ggl in sympathetic trunk -Pre vertebral ggl - celial, SMA/IMA -terminal ggl. - urinary bladdr & rectum - ! sweat glands use Ach-Ach(muscarinic) -adrenal medulla is a form of ganglion, no postsynaptic fibers. Only Ach nicotinic. Secrete epi/norepi -> bloodChromaffin cells -inc HR, CO, dilating bronchioles -blood from GI tract -> skeletal m. -pupil dilaiton Parasympathetic divison - rest and digest -CN III, VII, IX, X - 37910 -Ganglions near or within organs -Sacral outflow(pelvic sphlancnic) S2-S4 -pupil constriction -accomodation for near vision -bronchial diamete inc. resistance -inc peristalsis -erection -use acetylcholine on nicotinic and muscarinic Feature Cholinergic Nicotinic Cholinergic muscarinic Adenergic Alpha1 Adenergic Alpha2 Adenergic B1 Adenergic B2 Adenergi c B3 Info Autonomic Nn/N1 Skeletal m. Nm/N2 Only presynaptic Autonomic ggl M1 >Ca2+ release Myocardium M2 coupled K+ ch Smooth m./gland M3 Sweatglands Can be presynaptic at autocrine cells Postsynaptic at target cells in eye(dilator p) in fingers etc for constric presynaptic at target cell decrease release of norepi on sympathetic nerves in eye(dilator p) renin release not innervated present in A- venule shunts -dilate fat Structure Prefer: Ionchannels Ionotropic 7 subunit Metabotropic Metabotropic Norepi/epi Metapotropic Norepi/epi Norepi/epi equally Norepi/epi Norepi/e pi ANS part Sympathetic/Par asympathetic +skeletal m. Parasympathetic Sympathetic Sympathetic Sympatheti c Sympathetic Sympathe tic G type G-protein phospholipase C G-protein phospholipase C Agonist Ach Small dose of nicotine Acetylcholine Muscarine piloarpine Norepi phenazoline formoterol salbutamol Antagonist Large dose of nicotine Botulin Atropine Phentolamine Phentolamine Propranolol Metroprolol Propanolol Blocking-> curariform drugs block Ach binding Atropine -> Reduce diarrhea and dysapnea Blocked in atrial hypertension Prazosine Slows HR some vasoconstriction Stimulation- > Decreased HR Peristalsis etc Constrict airways calm breathing Sphincting Smooth m. Vasoconstriction GI + limbs Increased BP Nässpray stimulates for vasoconstriction -> less swelling GI tract relaxation Less secretion decrease cAMP Increase HR -Inc force of contraction + cAMP ++ cAMP vasodilation in bronchiole an skeletal m. -relax bladder and uterus -decrease GI motility ++ cAMP releases triglyc in up to 70% max excercise Bronchial Asthma Block by atropine Stimulate with B2 agonist -formosterol Choose specific If B1 also blocked heart pounding Arterial Hypotensio n Stimulate for vasoconstriction - norepi + give dopamine against decreased bloodf in glomerulus Stimulate for inc HR and force norepi/epi Ischemic heart disease Block for decreased 02 consumpti on less force o HR If B2 also blocked (nonspecific) difficulty breathing may occur Intestinal colic Block by atropine decrease peristalsis Fight/flight inc sweating AcH release decrease cAMP dilator pupillae constriction in limbs and GI tract sphincter activation less saliva inc. HR and force bronchodilation vasodilation in skeletal m. relax smoth m. detrusor m. shunt activatio Immodium against diarrhea act as an opioid stimulates K+ outflow -> hyperpolarizing, makes cell less prone to fire - less Ach released inhibits adenyl cyclase - less camp - less Ach released Decrease of cAMP promotes secretion All B-recetptors increase cAMP Increased cAMP will promote relaxation in smooth muscle, while promoting increased contractility and pulse rate in cardiac muscle. Junction between postganglionic autonomic neuron and effector(target) cell - neuroeffector junction A single postganglionic neuron can affect a large area of target tissue -Autonomic neurotransmitters are synthesized in the axon or body -More NT -> larger and stronger response -Enters by diffusion or metabolized in ECF & transported to other cells -Eg norepinephrine metabolized by MAO or repacked into vesicles Cocaine - an indirect agonist that blocks reuptake of norepi inte adenergic terminals -> prolonged excitatory effect Amphetamine - increase NE activity Anticholine esterase - block choline esterase (Ach degradation) Aterial hypotension - dopamine D1 agonist -> renal vasodinaltion The somatic motor division 1x neuron Somatic pathways are always excitatory -Cell bodies in ventral horn of spinal cord Neuromuscular junction - motor end plate AcH nicotinic receptor NAcHr receptor Similar to simple nicotinic but it binds to a-bungarotoxin too AP-> Ca2+ channel leak in -> Ach Release into synapse -> NacHr on motor end plate -> gated Na+ channels -> along T-tubules ->depolarization and contraction Drugs affecting neuromuscular junction Depolarizing - nicotine, metacholine -> prolonged depolarization -> spasm Non-depolarizing(Curariform drugs) - d-tubocurarine binds to N2 receptor prevent ACh from binding -> no excitation of m. cell possible -> death(suffocation) AcH esterase inhibitors - DFP - decrease AcH inactivation -> inc AcH cell exposure and inc response. Used as a chemical weapon Botulin(Botox) - inhibit ACh release from nerve endings. Management of myasthenia gravis & wrinkles -from clostridium botulinium -destroy SNARE- proteins Strycknos toxifiera - large plant. Currare block N2 cholinergic receptors -> no muscle depolarization Blue poison dart frog batrachotoxin -> irreversible opening of Na+ channels -> unceasing depolarization -> death Myasthenia gravis Disease in loss of Ach receptors on skeletal m. Autoimmune. No depolarization -> no contraction At rest axon terminal of motor nerve relases mini amount of AcH - miniature end plate potentials -Directly proportional to Ca2+ -Inversely proportional to Mg2+ MUSCLES CHAPTER 12-13 skeletal m. - striated, multinucleated. Stapedius m. smalles striated in body gluteus maximus - most massive latissimus dorsi - widest sartorius - longest -cells electrically isolated -hormone insensitive -40% body mass cardiac m. single nucleus striation, involuntary, intercalated disc gapjuncitons smooth m. single nucleus, non striated, involuntary, gapjuncitons -hormone sensitive Contractility - ability to shorten with generation of force Extensibility - stretching beyond normal length Elasticity - ability to return to original resting length after stretch Skeletal m. -Cannot contract without somatic motor neuron -their contraction is not directly influenced by hormones -flexors/extensors are antagonistic muscle groups Sarcoplasm Sarcolemma Myofibrils - one muscle fibers is like 100 myofibrils Sarcoplasmic retuculum SR - around each myofibril T-tubules - allow AP to flow from surface to interior rapidly Myosin has light chains and heavy chains- motor domain and actin binding site —> Thick filaments Actin G-actin to F-actin each G-actin has a myosin binding site —> Thin filaments Sarcomere Z-Z Thin filaments attach to Z-disc Thick filaments to M-line Muscle contraction -Force created by contraction - tension -Shrinks sarcomere Contraction is the active creation of tension Load opposes contraction Relaxation is the release of tension Titin - stabilizes myosin (TM) Nebulin - helps alligh actin (elli gick NA) - promotes strong acting-myosin interactions Actin-myosin sliding -I band and H zone disappears shortening muscle -Myosin pulls on actin like a rope hailing - power strokes -Myosin ATPase provide energy Ca2+ increases -> Ca bind to troponin-> troponin binds to tropomyosin that blocked actin binding sites on G-actin-> myosin can bind->power stroke Relaxed state just before power stroke - 90 degree cross bridge The rigor state - 45 degree cross bridge relative to filament No metabolism- no ATP -> muscles do not bind ATP -> rigor mortis the tightly bound state AcH released into synapse -> opening Na+ influx, K+ out -> end plate potential - Always above threshold AP is conducted along T-tubules opening Na+ channels AP in T-tubules alters DHP receptor DHPs open RyR Ca2+ release channels from SR ->Ca2+ release from SR Ca2+ binds to troponin allowing actin-myosin binding DHP-RyR - electrochemical coupling. No extracellular Ca2+ needed Note! In response to depolarization of T-tubule change of shape of DHPR is necessary for RyR activation while influx of Ca2+ is not Relaxation Ca2+ ATPase pumps Ca2+ back into lumen one contraction-relaxation cycle - a twitch latent period - between AP and muscle tension. Time for Ca2+ release and troponin binding -Resting muscle stores ATP in phosphocreatine binds -fast intensive -=2 dependent fatty acid - used in light exercise -O2 dependent glycolytic - heavy exercise Fatigue depends on not fast enough Ach synthesis and K+ release, an imbalance in membrane potential. ATP needed for -Na+/K+ ATPase -Contraction (power stroke) -relaxation - active pumping of Ca2+ back to SR Treppe effect -Graded response -In muscle rested for a prolonged period -Each contraction is stronger than previous until equal after a few stimuli Slow twitch fibers - myoglobin rich red m. fiber. better blood supply Oxidative. Fatigue resistant. Smaller diameter Fast twitch FOG IIA - large diameter - glycolytic rapid ATP split - contain myosin - white fibers, fewer and smaller mitochondria Fast twitch FG IIB - Pump Ca2+ faster. Fatigue most easily Oxygen concentration is a factor - depend on myolglobin (has high O2 affinity) Fatigue Psychological - emotional state Muscular - ATP depletion Synaptic - neuromuscular junction, lack of AcH The tension a muscle can generate is directly proportional to number off cross bridges between thin and thick filaments -why optimal sarcomere length exists ! Single twitch tension is determined by sarcomere length Then force generated by contraction can increase by increasing frequency at which APs stimulate muscle fibers No time to relax completely -> summation Unfused tetanus - m. fibers partially relax - some Ca2+ can be recycled between contraction complete tetanus - no relaxation, flat line Allo or none law for muscle fibers -Contraction of equal force in response to each individual AP when they arrive at sufficiently long intervals Graded for whole muscles Force of contraction of whole muscle range from weak -> strong depending on stimulus strength. Motor unit Somatic motor neuron + fibers it innervates(one fiber type only) more fine MU for e.g eye, bigger for like thigh There are fast twitch MU and slow twitch MU -Each alpha motor neuron innervates a motor unit -all cells in an MU contract simultaneously -small MU are recruited first(low threshold, size principle) Graded force/contraction depending on -Changing types of active MU -And changing number of MU responding at any given time Done by recruitment We are able to maintain constant tension due to variations in MU. The fatigued ones overlapped by pigga ->summation of force= function of stimulation rate FINAL COMMON PATHWAY: Alpha motor neurons collecting inputs -> neuromusclular junction convergence of many neurons onto a single motor neuron IsoTONIC contraction - creates force and moves load Sarcomeres shorten more but elastic elements are already stretched -> shortening of the muscle = concentric Eccentric - tension maintained but muscle lengthens Isometric contraction - force without moving load - static Creates force but do not shorten, elastic elements. Sarcomeres still shorten(contract) but the elastic elements streches to maintain constant length -> Firm and ready for action at all times ->postural muscles of body ATP for muscle contraction Creatine phosphate 3-15sek Anaerobic respiration 10sek-2min- glc -> ATP + lactic acid Aerobic respiration - 38ATP/1 glc Gravity produces tonic muscle tension Smooth m. phasic- usually relaxed tonic - maintaining some level of tension - e.g sphincters single unit smooth m. - linked by gap junctions - multi unit - cells not electrically linked, act independently - like iris/ ciliary m. most smooth m. are single unit - visceral -actin myosin interaction -contracts by increase Ca2+ levels in cytosol -smooth m. relax and contract more slowly -require less ATP to generate and maintain force -no fatigue -no sarcomeres -single nucleated -higher sensitivity to ion conc. changes -tends to contract in response to sudden stretch(myogenic autoregulation of bloodflow) -amplutude of contraction constant - muscle length varies Myosin phosphorylation controls contraction Ca2+ binds to calmodulin -> phosphorylation of myosin light chain(kinase) Myosin ATPase -> contraction MLCP control Ca2+ sensitivity Dense bodies Autonomic control -Antagonistic control by sympathetic/parasympathetic -Bloodvessels(symp) and sphincters under tonic control -Linked to G-protein coupled receptors -Phospholipase C-> DAG relase of Ca2+ -> increase of MLCK and MLCP -> contraction -adenyl cyclase-> increase of cAMP -> increase of myosin phosphatase activity -> relaxation Control of body movement and reflexes somatic reflexes - somatic motor neurons autonomic reflexes - autonomic neurons spinal reflexes - integrated in spinal cord cranial reflexes Primitive reflexes/newbron - originate in brainstem, disappear in normal brain development. CP kids may retain these Innate reflexes - born with it, may disappear Learned reflexes Monosynaptic reflex - A sensory afferent synapse direcly on a motor neuron. Only somatic motor reflexes Polysynaptic - at leas one interneuron, all autonomic reflexes, 1x afferent, 2x efferent Superficial reflexes - stimuli of mucus/skin - corneal, cremasteric, suckling, plantar Deep reflexes - stretch reflexes Segmental - stretch reflex Intersegmental - flexion withdrawal - polysynaptic reflexes suprasegmental - swallowing Most reflexes does not need to involve brain but brain can: Inhibit by increasing electronegativity (hyper polarize) Facilitate by decreasing electronegativity (depolarize) The reflex arc - basic functional unit of our ns. Autonomic reflexes -Visceral -Polysynaptic -could be spinal BUT modulated by excitatory/inhibitory signals from brain, like urination -Higher control of a spinal reflex - a learned response(?) -tonic activity Skeletal m. reflexes Muscle info -> CNS -> Response: Contraction leas to activation of somatic motor neurons OR Relaxation - a result from absence of excitatory input by somatic motor neuron - they are inhibited Proprioreceptors(sensory) - info of position and effort. Input to CNS via sensory neurons. CNS integrates via excitatory/inhibitory interneurons. Can become perception in cortex. Somatic motor neuron - carry output signal. Neurons innervating skeletal m. - called alpha motor neurons innervates extrafusal motor fibers The 3 proprioreceptors 1. Muscle spindle -stretch receptors -> causes stretch reflex - MYOTATIC REFLEX -paralell to extrafusal muscle fibers -each m. spindle in a capsule enclosing intrafusal m. fibers(lack myofilaments centrally, smaller and parallel to extrafusal fibers and can be stimulated by gamma motor neurons) -Has contractile ends but central region lacks myofibrils -Central region is excitable by 1. stretching of entire m. or 2. stretching of contractile ends(m. length remain constant!) -Innervated by gamma motor neurons Funciton -reflex for muscle tone -transducers(sensors) of muscle stretch, amplitude and velocity) -indirect not voluntary initiator of m. contraction - patellar reflex Gamma neuron stimulated ->The noncontrictile part is wrapped in sensory nerve endings -> info into sensory neurons -> spinal cord -> alpha motor neurons innervating that m. ! Resting muscle has enough stretch to activate this tonic control -> muscle tone This is also leads to reflex contraction to precent overstreching = stretch reflex. Stretch reflex maintains muscle tone and posture ! Prescence of gamma motor neurons keeps spindles active no matter length. Muscle contraction by alpha motor neurons while gamma MN keeps spindle tense at contractile end. Muscle spindle reflex: Putting a load in 90degree elbow hand - hand will fall and the set back into normal position due to muscle spindle. Types of fibers within muscle spindle: Type Ia - primary afferent fiber excited by both nuclear bag and chain fiber. 17mikrom in diameter-. Dynamic response to stress. short stretch. Excite alpha-mn via Monosynaptic pathway highest velocity Type II - secondary afferent is only excited by chain fiber (thinner). 7mm. Static response to stress. Sustained stretch. mono and polysynaptic pathway Both excite alpha motor neurons of that muscle Ia and II afferentes secrete glutamate during motor activity both alpha and game motor neurons activated -> a-g coactivation 2. Golgi tendon Junction of tendon and muscle fiber -Active during isometric contraction(no load moved, force but do not shorten) hold a glass of water, yoga -Reflex Causes relaxation - prevent överansträngning -Free nerve endings inside CT capsule embedded in collagen fivers -Embedded in collagen fibers Ib fibers - do not synapse directly on motor neurons GTO much less sensitive to muscle stretch than stretch repectors - nerve endings are encapsulated Muscle contraction tightens the fibers, squeezing nerve endings that fire afferents -> spinal cord-> inhibitory interneurons activation-> decreased excitatory output in alpha motor neuron->decreased contraction This reflex slows muscle contraction an prevents over contraction ! ! Think back on holding the load in 90 degree angle, if the load becomes heavier then the tension the muscle can develop -> inhibition of alpha motor neurons-> relaxation and the arm falls. Important to protect the muscle fire from damage! Deep tendon reflex -opposite of stretch reflex -activate GTO -> inhibitory interneuron -> decrease alpha neuron fire -stimulate contraction of antagonistic muscle(active & elasticity) ->contractive m. relaxes Passive stretch of m. -spindle activated -> contraction of extrafusal m. fibers(stretch reflex) -not stretched enough for GTO Active contraction - central activation of alpha MN-> contraction of extrafusal m. fibers -muscle spindle relaxed(inactivated) GTO activated - causes relaxation Active contraction with gamma contraction -intrafusal and extrafusal fibers contract Ia and II afferents -GTO activated but inhibition too weak -when load becomes too great inhibition is strong enough and reverse mitotic reflex starts(muscle relaxation) 3.Movement around joints - diverging and converging pathways - myotatic unit -simplest reflex in myotatic unit - monosynaptic stretch reflex 1- sensory neuron from spindle 2. alpha motor neuron to muscle Knee jerk reflex 1.monosynaptic stretch reflex of quadriceps - end of the stretch reflex is monosynaptic 2. reciprocal inhibition(polysynaptic) of antagonist (hamstring) 1. Tap-> stretch-> spindle activation-> AP in sensory neuron->synapse in spinal cord-> efferent motor neuron->contraction of quadriceps — monosynaptic 2.synapse in spinal cord also activate inhibitory interneuron -> synapse to inhibit motor neuron in hamstring(relaxation) —polysynaptic Flexion reflexes - limb away from panful stimuli -Polysynaptic -Rely on divergent pathways in spinal cord -Takes longer time than spinal reflex -Both relaxation of antagonist and alpha motor neuron activation -> flexion Noci(pain) receptor->affferent neuron->spinal cord->divergence: 1.excitatory interneurons - alpha MN contraction -> flexion 2.inhibitory interneursons to cause relaxation of antagonist Flexor reflexes especially in e.g legs - accompanied by crossed extensor reflex: -Maintains balance when one foot is off the ground -> extensors contract in supporting leg, relax in flexed leg Our natural gaair pattern, crawl, walk, run MOVEMENT Reflex movement -Least complex -Primarily spinal cord -Sensory input can reach brain for coordination Postural reflex -Integrated in brainstem -Input from visual, vestibular and muscular proprioception -Reason for like blind seeing -Sensory feedback is used to refine reflex movement Voluntary movement -Integrated in cerebral cortex -initiated without external stimuli -Can become reflexive -Muscle memory - developed when unconscious brain reproduce voluntary movements. Rythmic movement -Walking/running -Combination of reflex/voluntary -Cerebral cortex initiates/terminates ! Central pattern generators in-between — Animal paralyzed by spinal injury cannot initiate walk but if put on a treadmill CPGs will produce movement :) ! Maintnance of posture include all of the above mentioned movements CNS integrates movement Spinal cord - integrates spinal reflexes and has CPGs - info from proprioreceptios Brainstem/cerebellum - Central postural reflexes + hand/eye movement - info from proproiR (signals from vestibular apparatus co directly to cerebellum) Cerebral cortex/basal ggl - Voluntary movement A pitcher decides ot throw a ball AP in interneurons of corticospinal tract Motor cortex -> spinal cord onto somatic MN Contralaterall crossing in medullary pyramid (in pyramidal tract) ->lateral corticospinal tract Neurons from basal ganglia - extrapyramidal tract noncrossing fibers - anterior corticospinal tract Parkinsson Proves basal ganglia has o role in body coordination Disrupt in release of dopamine Tetanus COntracted muscle paralysis by clostridium tetani. Lecture CNS -stimulus on free nerve endings -> graded potentials Gray matter in CNS -cortex -nuclei -centers White matter -tracts -columns - several tracts -Pathways - ascending and descending PNS gray matter - ganglia PNS white matter - nerves Divergence -broad distribution of specific input. pre and post Convergence -several neurons synapse on same postsynaptic neuron summation-> response Serial processing neuron -> next neuron One part of CNS to other Parallell processing Divergence first then several neuronal pools process same information ->many responses at the same time Reverbeation 1x neural pool/intermediate pool sends a positive feedback to keep chain of neurons active.. Will continue into stimuli breaks/fatigue Presynaptic inhibition 3x target cells One has a inhibitory interneuron that synapses (hyper polarizing) -> no response in A ->Response in B and C Somatosensory pathway -Relayed ot brain/spinalcord via ascending pathways Specific: 1 typ of receptor 1type of stimulus Specific cortex areas Nonspecific More than one sensory unit To brainstem, reticular formation, thalamus FLow Receptor->1st order N(dorsal root ganglion)->2nd order N(spinal cord/brainstem)->3rd N(thalamus)->Somatosensory cortex(312) Somatic part of sensory system transmit sensory information from skin, muscles, joints to CNS -all levels of spinal cord -reticullar formation, brainstem, midbrain -cerebellum,thalamus, somatosensory cortex Receptors from dorsal root Pacinian corpuscle - vibration, pressure muchanoreceptor Muscle spindle, golgi tendon organ Encapsulated endings ! Free nerve endings form lateral division Primary somatosensory cortex 312 postcentral gyrus parietal lobe + sensory assosciation area -ascending pathway in spinal cord - dorsal column (gracilis and cuneus) Column in spinal cord - white matter (dorsal, ventral, lateral) Horn - gray matter (posterior, lateral, anterior) Descenting tracts(motor) Primary moter cortex, precentral gyrus € premotorcortex 6 -> skeletal m. movement Motor neurons in ventral horn of spinal cord Direct pyramidal tract (corticospinal) -initiation on motor/premotor cortex -upper motor neuron motor cortex -> brainstem motor cortex -> spinal cord -lower motor neuron - alpha motor neurons voluntary movement and tone -only 3% Betz cells -80% cross at medullary pyramid -> lateral corticospinal tract -20% do not cross (eventually in spinal cord) -> anterior corticospinal tract. to postural muscles —most axons synapse with contralateral interneurons in spinal cord but some make monosynaptic connections to A/G motor neurons Babinski respone -damage to corticospinal tract. Fanning of toes planter reflex Corticospinal - to muscles innervated by spinal motor neurons Corticobulbar - motoroutput to muscles of face, tongue, throat Indirect extrapyramidal tract -motor cortex -projections via brainstem nuclei -Neurons from basal ganglia - extrapyramidal tract -unconscious movemet - posture, balance-muccle tone Rubrospinal tract - red nucleus. Flexors excitements, inhibit extensorz Vestibulospinal tract - uncrossed bilateral - inc m. tone by gamma loop activation. no free fall while standing -Tectospinal tract - crossed -Terminates in spinal cord via interneurons which contact alpha and gamma motor neurons -Fibers which influence axial m. are crossed -Fibers for the limbs - mostly uncrossed ->Permits independent control of the limbs and axial muscles. Manipulation can proceed while posture is maintained Bell magendive law Anterior/ventral spinal nerve roots = motor Posterior/dorsal nerve roots = sensory The anterior spinal nerve roots contain only motor fibres and posterior roots only sensory fibres. Stycknine poisoning - blocks inhibitory signals by competing with the inhibitory neurotransmitter glycine in spinal cord -> excitatory state Easily activated muscles -> Muscle spasm. Death. In rat poising glycine - inhibitory in spinal cord glutamate - excitatory myotome same as dermatome but for motor output(muscle groups) spinal schock - areflexia early - no stretch receptor, no sphincter tone, no sympathetic activity on smooth ml weeks - upper motor neuron signs develop, gradual reflex dec, some sphincter and ere tile, no voluntary control Lessons from practice tests Renshaw cells are inhibitory interneurons found in the gray matter of the spinal cord, and are associated in two ways with an alpha motor neuron. They receive an excitatory collateral from the alpha neuron's axon as they emerge from the motor root, and are thus "kept informed" of how vigorously that neuron is firing.They send an inhibitory axon to synapse with the cell body of the initial alpha neuron and/or an alpha motor neuron of the same motor pool. In this way, Renshaw cell inhibition represents a negative feedback mechanism. A Renshaw cell may be supplied by more than one alpha motor neuron collateral and it may synapse on multiple motor neurons. -Renshaw cells act to inhibit sudden movements. Inhibit-inhibition af antagonistic muscle. -recurrent inhibition -control degree of efferent signal sent to the muscle -Descending cortical pathways modulate renshaw cells Type 1a muscle fibers - in muscle spindle sensory. respond to change in length and velocity type Ib in golgi tendon type II - fire when muscle is static ATP is directly involved in relaxation of skeletal muscle Activation of renshaw cells -> increased permeability to Cl- ions and decreased AP in alpha motor neurons The CSF has a lower glucose level than plasma Alpha 2 motor neurons has low recruitment threshold - alpha 1 has high. Remember size principle - small motor unit and low threshold activated first. Final motor pathway = alpha motor neuron and ad the end of that pathway we have: neuromuscular junction Fast depolarization caused by voltage gates K+ channels ? In monosynaptic spinal reflexes their afferents and efferents are contained within same spinal nerve the most used muscle fiber type in body are slow muscle fibers flexion reflex involves more motor neurons than stretch reflex activation of gamma motor neurons stiumulates activation of alpha motor neurons Inhibitors tetrodoxin(irriversible) - blocks Na+ channels - no AP Lidocaine(reversible) - blecks Na+ channels - no AP Bartrachotoxin - opens Na+ channels irreversibly - blue froggy Ach esterase breaks down acetylcholine to acetyl + choline Ach-esterase inhibitors ->spasm and hyperactivity of parasympathetic division Irreversible: flourophosphate, disopropyl Reversible neostygmine, phosphostygmine Botulin - prevents release(exocytosis) of Ach Curare - blocks the binding of Ach->no depolarization Strychnine - inhibits glycine ”inhibits inhibition” -> excitation > uncontrolled convolusions and respiratory arrest. On frog on LAB Atropne - blocks muscarinic receptors, inhibit parasympathetic neurons Ouabain - Na+/K+ ATPase inhibitor ! metroprolol - is B1 specific neuron resting membrane potential = -70mV Muschle fiber resting membrane potential = -90mV -Depolarization is not contraction! -ATP needed both for contraction and relaxation -Duration of AP in skeletal m. much shorter then duration of contraction - why summation is possible https://www.dropbox.com/sh/7wd22woosu6ald2/AADtMrSAoLPmCyzXrAWhPy0Ya/physiology/Physio/PHYSIOTESTS/Physio/Tests%EF%80%A 2Exams%205/PAT1/PAT1_-_summation.docx?dl=0 receptors sense a response via graded potentials Somatotropic organization in ventral horn: proximal muscles toward center extensor most anteriorly small MU - low threshold - activated first slow MU fiber lower threshold muscle tone cannot be voluntarily controlled rubrospinal tract innervate flexor muscle - intact in decorticate but not decerebrate postion? upper motor neuron damage - spastic, hyperreflex lower motor neuron - flaccid, no reflexes Activation of renshaw cells -increased permeability of alphamMN to cl- ions FALSE latency time of autonomic reflexes is the time needed for electromechanical coupling of ganglion cells Skeletal m. has nicitinic cholinergic receptors atropine block muscarinic During normal movement red muscles fibers are recruited before white muscle fibers In smooth m. increased levels of cAMP favors muscle relaxation Labs Human monosynaptic reflexes -Patellar -Achilles -Biceps and triceps Human polysynaptic -Flexion reflex -Abdominal reflex -Planter reflex(Babinski sign) Propranolol test - proving parasympathetic influence on HR Beta blocker non selective
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most fluid are intracellularisoosmotic conc.
Na+/K+ ATPase depends on:-Na conc inside-K+ outside-Energy supply(ATP)-Temprature-Inhibitors? Ouabain
RM potential-70mV for majority of neurons
Threshold potential-55mV
Equilibrium potentialhypothetical potential difference across cell membrane at which net cross of ions due to gradients would be equal to 0
Sensory neuron-graded potentials-myelinated/unmyelinated axons
Chapter 8 - APs, GPs etc.
Axon - transmits electrical impulse to distal end where electrical signal -> chemical via:Neirotransmitter, neuromodulator,(neurohormone)-Axons lack RER and ribosomes hence all proteins are synthesized in soma for axonal transportSlow and fast axonal transport
Glial cells - support for neuronsPNS: Schwann cells - myelination (1 node 1 Sch cell)Satellite cells - ganglions CNS:Oligodendrocytes - myelination (several nodes)Microglial cells - immune responseAstrocytes - blood brain barrierEpendymocytes - neura stem cells + compartments
Nerve and muscle cells are excitable tissuesVm - resting membrane potential-Uneven distribution of ions across the membrane-Mainly due to K+-90mV or - 70mV in resting neuronNa+ in depolarize - too much K+ out hyperpolarize(become more negative)Hypopolarize(become more +/ närmare 0 / more excitable)
1. Mechanically gated ion channels -In sensory neurons open to physical forces like pressure or stretch2.Chemically gated ion channelsRespond to ligands(neurotransmitters/neuromodulators) & intracellular signal molecules.3.Voltage gates ion channels-Resoond to change in resting membrane potential - depends on threshold—>Depolarization opens fast gated Na+ channels and then K+ channelsThis can work as a swing door - swings back closed when electrical signal passedIt can also be inactivated - works like an automatic timed door (off button)
Net flow of ions depend on electrochemical gradient Graded potentials -Variable in strength-Loose strength on the way (stone in water)-If the stone is big then more likely to fire AP-> amplitude is directly proportional to strength of triggering event-Occurs in cells body(soma)-Loose strength due to K+leak and cytoplasmic resistanceAction potential-Large depolarizations-Do not loose strength -Rapid signalling over long distances -Works like a domino-Peaks at + 30mV-Equilibrium for Na+ at +60mv?-Falling phase: increase of K+ leak - inc negativity and fall of AP-SPeed depends on diameter and ions leakage - large and myelinated -> fastest conduction
Graded Potential Action potential
Input signal Conducting signal
In cell body trigger zone->axon
MechanicalChemical or voltage G
voltage gated
Na+ K+ Cl- ions Na+ and K+
DepolarizingHyperpolarizing
Depolarizing
Summation All or none
Gated channelsNO threshold
threshold -> open ion chan
no minimumfor initiation
threshold -55mV needed
no refractory period refractory period
strength by frequency No AP in refractiory period
Na+ channels has two gatesActivation gate and deactivation gate-55mV - Activation gate opens0mV - Na+ enters+30mV - inactivation gate closes (peak of curve)Repolarization - activation gate closes and inactivation gate open - reset to original state
Absolute refractory periodNa+ channels must reset to original position (1-2 millisek)-> AP cannot fire now and no moving backward
The relative refractory period - Larger than normal stimulus can trigger AP
At depolarization site of axon + inside -outsideNomal: - inside ++outside
Nodes of ranvier has high concentration of Na+ channels-> Saltatory conduction, like jumpingIn demyelinating diseases like MS - conduction is slowed
Chemical factors-Neurotoxins blocking Na+ channels, neurotoxins fails to pass signal to postsynaptic neuron-Botulin?-Snake poison?
Normal K+ conc = 3.5-5mmol/LHypokalemia-Increased electronegativity-Farther away from threshold-Presents as muscle weakness
Hyperkalemia-Decreased electronegativity (more + cell) - K+ will not leak out as fast(osmos)-Hypersensitive neurons-Fire AP to smaller GP
Hypernatremia - hypersensitive neuronsHyponatremia - muscle cramps
Electrical synapses-Mainly in CNS-Smooth m.-Gapjunctions allow chemical signaling molecules to pass electrically
Chemical synapses-Electrical signal becomes a chemical neurocrine-Neurotransmitter - rapid and local in one synapse-Neuromodulator - can be synaptic and non synaptic, slower acting. Auto/paracrine
Neurohormones bind to ionotropic receptors or metabotropic(G-protein coupled)Circulate in blood
NeurotransmittersReleased from vesicles on demand by exocyotosis into synaptic cleftBotulin and other toxins block this exocytosis apparatus
Glutamate - main excitatory in CNS, act on ionotropic and metabotropic receptors. aspartate is another one excitatoryGABA - Main inhibitory in brain made from glycineGlycine - main inhibitory in spinal cord - Cl- channels for hyperpolarizationSupstance P - pain pathways and pain relier(opiods)ATP/AMP - Can act as Nts, purines. In CNS and heartNitric Oxide -Acetylcholine-Epinephrine-Norepinephrine-
Depolarization leads to Ca2+ influx along gradient -> binds to proteins triggering exocytosis-> Nt released into synaptic cleftThen vesicles are endocytosed and retrogaededly transported back.
AcH becomes Acetyl + choline by Acetylcholine esteraseMAO breaks down norepi in mitochondria
-Ability for neurons to change activity at synapses - synaptic plasticity
2nd msg metabotrppic by neuromodulatorsFast ion channels by neurotransmitters
Cell response of postsynaptic neuron determined by summed input from presynaptic neuronEPSP - excitatory depolarization Na+ or Ca2+ inflowIPSP - inhibitory hyperpolarization - Cl- inflow or K+ outflowSuprathreshold - EPSP> IPSP -> AP
At postsynaptic cellSpatial summation: graded potentials arrive at different regions, summedE.g inhibition - 3x convergence: 2x EPSP + 1x IPSP -> subthreshold sum! Inhibition does not always require multiple neurons - if IPSP/EPSP arrive close in time they can be summed
Temporal summation - GPs close in timeSpatial + temporal summation = postsynaptic integration
Presynaptic inhibition-Inhibitory neursons decrease amount of neurotransmitter release(depolarization)-hyperpolarizationMore precise than postsynaptic inhibition-> Target response changeThis is all done by neuromodulators -> no response or weaker response in target cell A
Upon injury to a neuron-proximal stump regenerates by support of glial cells-distal stump macrophaged
Factors effecting nerve conduction-pressure - tingling, CP ulnar nerve-decreased temp -> reduced pain. if ice crystals in cell, irreversible-toxins-etherethyl ethanol - destroy lipid bilayer, on lab, irreversible
Chapter 6 - CommunicationLocal communicationGap junctions-Cytoplasmic bridges between adjacent cells-2x connexins -> connexons(protein channel) that opens/closes-For small ions and molecules:ATP amino acids-The only mean by which electrical signals pass directly from cell->cell
Contact dependent signalsSurface molecule of one cell ->membrane protein of another cellIn nerve development and immune systemParacrine: Cells in vicinity. Histamine acts this wayAutocrine - cell act upon self
Long distance - Endocrine systemChemical - hormones in bloodIn contact with all cells - the ones with correct receptors mediate a response
CytokinesLocal and long distanceSynthesized in response to stimuliAct broader than hormones, produced by all cells, made on demand
A cell can respond to the signal if it has appropriate receptorLigand->receptor->activation->intracellular activation->synthesis of target proteins->response
RECEPTORSLipophilic - signalling molecules can diffuse through membrane and bind to nucleus/cytosol membrane. Common in gene activation. Usually hormones
Lipophobic - Ligand need receptor protein in membrane. -> Rapid response-Ligand gated channel-Gprotein coupled receptor - a transducer - activates 2nd msg system-Receptor enzyme-Intergrins
G-protein coupled receptors-Pass 7x across membrane-Inactive G-protein bound to GDP-GDP->GTP activates Gprotein ligand binds->phospohorylating->activation-Amplifyers: adenyl cyclase and phospholipase C
Lipophobic G-protein - cAMPAdenyl cyclase converts ATP-> cAMPcAMP activates protein kinase A - PKA->phosphorylation and signal cascade
Lipid derived G-protein - phospholipase CPhospholipase c converts a membrane phospholipid intoDiaglycerol - activates PKCIP3 - Leaves membrane, RyR Ca2+ channel on ER -> C2+ release in cytosol
IntegrinsAnchored to cytoskeletonImportant in blood clotting
Ligand gated channelsFastestIon channels along gradients
Orphan receptors - no known ligand- Eicasoid signal molecules from archidonic acidLeukotriennes??
SIGNALING MOLECULES/LIGANDSCalcium-Voltage/Ligand/Mechanically gated Ca2+ channels-Released intracellularly by IP3-Stored in ER-Ca2+ to calmodulin - enzyme activity in smooth m.-Ca2+ to troponin -> m. contraction-Ca2+ to channels altering their state (Ca2+ activated K+ channel)
NO - dilates bloodvessels. cGMP formation. Neurotransmitter in brainCO-toxicH2S - relaxes bloodvessels in cardiovascular system
Usually cell response depends on receptor not on ligandLigand -> response A in tissue Xresponse B in tissue YThis is explained by ligands binding to different isoforms - e.g adenergic receptors.Epinephrine to alpha receptors - vessel constriction Epinephrine to Beta receptors - vessel dilation
Also different ligand can bind to same receptornorepi/epi in fight/flight respond can bind to both alpha and beta receptors
Antagonist - ligand that occupy/blockAgonist - ligand that activate
Down regulation - decrease in receptor on surface by endocytosis. Too much agonists e.g. Can also be done by desensitization (phosphorylation of B receptor)Drug tolerance can partly be explained by down regulation - not as effective response to high ligand concentration. Up regulation - Less internalization, hypersensitive receptors. Response to too low ligand concentration
Homeostatic reflex pathways-Some systems are under tonic control - signal always present, volume up/down-Systems not under tonic control are under antagonistic control - e.g autonomic control of HR-Chemical signals having opposing effects - antagonistic-An antagonistic signal in one tissue may be cooperative in other
Sphincters are under tonic controlOther smooth m.-undre antagonistic control
Reflex control pathwayStimilus->sensor/receptor->input signal -> integrating center -> output signal ->target -> response
Stimilus - change of variable (02, BP)->sensor/receptor - constantly monitors environment of variable->input signal - sensor sensed change, sends a signal to reflex integrating center-> integrating center - compares input with set point-> output signal - initiated if variable changed out of range. sends efferent chemical/elecrtical signal to->target - effector cell that carries out appropriate-> response
! Sensory receptors respond to changes in environment not the same as protein receptorsCentral receptors - brain, eye, ear , nosePeripheral receptors - in skin, internal organs etcAll sensors has a threshold, if stimuli is below - no response
Integrating center in endocrine reflexes - the endocrine cell itselfIn CNS - brain and spinal cord
If there is a single stimulus IC has a simple taskUsually multiple - IC sorts out what is most important’Output is always electrical and chemical by efferent neuron in neural reflexesSecreted in blood by endocrine R
The cellular response might be different from systemic response to reflexE.g vasodilation of cells causes systemic response of increased bloodflow
Neural reflex Endocrine reflex
Specifity 1x neuron specific target Lot of exposed cells,need specific receptor
Nature elecrical & chemical chemical into blood
Speed rapid slower
Duration of AP short can be longer with neuromodulators
longer response
Coding for identical signalintensity:frequency of signal
intensity:amount of hormonesecretes
These 2 reflex systems better viewed as a combo not two separate systemsComplex reflex control centers has more than one integrating center
Simple endocrine pathwayEndocrine cell is both censor and IC ->hormone releaseNo input needed-Target is any cell with appropriate receptor E.g insulin secretion
SImple neuronal reflex - knee jerk
Neurohormone reflex - identical to neural except neurohormone travel in bloodE.g breastmilk - oxytocin reflex
Autonomic nervous system
PNS efferent divisionSomatic motor neurons - skeletal m. controlAutonomic neurons - smooth m., cardiac m., glands, adipose tissue
Autonomic division-involuntary and self governing-two efferent neurons CNS->GGL GGL->TISSUE-Divergence! 1 preggl neuron synapse with 8-9 post-> 1 CNS signal effect a lot of target cells simultaneously-Cell bodies in lateral horn on spinal cord
Peripheral ganglions has neurons as small integrated centerstechnically a reflex could be integrated here
Antagonistic control - hallmark for ANS! Exceptions are sweat glands, smooth m. of blood vessels and sphincters - sympathetic tonic control
Sympathetic division - fight/flight-T1-L2-Sphlancninc nn.-Use acetylchole(nicotinic) pre & norepinephrine(adenergic) post-Paravertebral ggl in sympathetic trunk-Pre vertebral ggl - celial, SMA/IMA -terminal ggl. - urinary bladdr & rectum- ! sweat glands use Ach-Ach(muscarinic)-adrenal medulla is a form of ganglion, no postsynaptic fibers. Only Ach nicotinic. Secrete epi/norepi -> bloodChromaffin cells-inc HR, CO, dilating bronchioles-blood from GI tract -> skeletal m.-pupil dilaiton
Parasympathetic divison - rest and digest-CN III, VII, IX, X - 37910-Ganglions near or within organs-Sacral outflow(pelvic sphlancnic) S2-S4-pupil constriction-accomodation for near vision-bronchial diamete inc. resistance-inc peristalsis-erection-use acetylcholine on nicotinic and muscarinic
Feature Cholinergic Nicotinic
Cholinergic muscarinic
Adenergic Alpha1
Adenergic Alpha2
Adenergic B1
Adenergic B2 Adenergic B3
Info Autonomic Nn/N1
Skeletal m. Nm/N2Only presynaptic
Autonomic ggl M1>Ca2+ release
Myocardium M2coupled K+ ch
Smooth m./gland M3
Sweatglands
Can be presynaptic at autocrine cells
Postsynaptic at target cells
in eye(dilator p)in fingers etc for constric
presynaptic at target cell
decreaserelease of norepi onsympatheticnerves
in eye(dilator p)
renin release
not innervated
present in A-venuleshunts -dilate
fat
StructurePrefer:
IonchannelsIonotropic
7 subunitMetabotropic
MetabotropicNorepi/epi
MetapotropicNorepi/epi
Norepi/epiequally
Norepi/epi Norepi/epi
ANS part Sympathetic/Parasympathetic+skeletal m.
Parasympathetic Sympathetic Sympathetic Sympathetic
Sympathetic Sympathetic
G type G-protein phospholipase C
G-protein phospholipase C
Agonist AchSmall dose of nicotine
AcetylcholineMuscarinepiloarpine
Norepiphenazoline
formoterolsalbutamol
Antagonist Large dose of nicotineBotulin
Atropine Phentolamine Phentolamine PropranololMetroprolol
Propanolol
Blocking-> curariform drugsblock Ach binding
Atropine ->Reduce diarrhea and dysapnea
Blocked in atrial hypertensionPrazosine
Slows HR some vasoconstriction
Stimulation->
Decreased HRPeristalsis etc
Constrict airwayscalm breathing
SphinctingSmooth m. Vasoconstriction GI + limbsIncreased BP
Nässpray stimulatesfor vasoconstriction-> less swelling
GI tract relaxationLess secretiondecrease cAMP
Increase HR-Inc force ofcontraction+ cAMP
++ cAMPvasodilationin bronchiolean skeletal m.
-relax bladderand uterus-decrease GImotility
++ cAMPreleases triglycin up to 70% maxexcercise
Bronchial Asthma
Block by atropine Stimulate withB2 agonist-formosterol
Choose specificIf B1 also blocked heart pounding
Arterial Hypotension
Stimulate for vasoconstriction - norepi
+ give dopamine against decreased bloodfin glomerulus
Stimulatefor incHR andforcenorepi/epi
Ischemic heartdisease
Block for decreased 02 consumption
less force o HR
If B2 also blocked(nonspecific)
difficulty breathing may occur
Intestinal colic
Block by atropinedecrease peristalsis
Fight/flight inc sweatingAcH release
decrease cAMP
dilator pupillae
constriction inlimbs and GI tract
sphincter activation
less saliva inc. HRand force
bronchodilation
vasodilation inskeletal m.
relax smoth m.detrusor m.
shunt activatio
Immodium against diarrhea act as an opioidstimulates K+ outflow -> hyperpolarizing, makes cell less prone to fire - less Ach releasedinhibits adenyl cyclase - less camp - less Ach released
Decrease of cAMP promotes secretionAll B-recetptors increase cAMP
Increased cAMP will promote relaxation in smooth muscle, while promoting increased contractility and pulse rate in cardiac muscle.
Junction between postganglionic autonomic neuron and effector(target) cell - neuroeffector junctionA single postganglionic neuron can affect a large area of target tissue
-Autonomic neurotransmitters are synthesized in the axon or body-More NT -> larger and stronger response-Enters by diffusion or metabolized in ECF & transported to other cells-Eg norepinephrine metabolized by MAO or repacked into vesicles
Cocaine - an indirect agonist that blocks reuptake of norepi inte adenergic terminals -> prolonged excitatory effectAmphetamine - increase NE activityAnticholine esterase - block choline esterase (Ach degradation)
Aterial hypotension - dopamine D1 agonist -> renal vasodinaltion
The somatic motor division1x neuronSomatic pathways are always excitatory-Cell bodies in ventral horn of spinal cordNeuromuscular junction - motor end plate AcH nicotinic receptor NAcHr receptorSimilar to simple nicotinic but it binds to a-bungarotoxin too
AP-> Ca2+ channel leak in -> Ach Release into synapse -> NacHr on motor end plate-> gated Na+ channels -> along T-tubules ->depolarization and contraction
Drugs affecting neuromuscular junctionDepolarizing - nicotine, metacholine -> prolonged depolarization -> spasmNon-depolarizing(Curariform drugs) - d-tubocurarine binds to N2 receptor prevent ACh from binding -> no excitation of m. cell possible -> death(suffocation)AcH esterase inhibitors - DFP - decrease AcH inactivation -> inc AcH cell exposure and inc response. Used as a chemical weaponBotulin(Botox) - inhibit ACh release from nerve endings. Management of myasthenia gravis & wrinkles-from clostridium botulinium-destroy SNARE- proteins
Strycknos toxifiera - large plant. Currare block N2 cholinergic receptors -> no muscle depolarizationBlue poison dart frog batrachotoxin -> irreversible opening of Na+ channels -> unceasing depolarization -> death
Myasthenia gravisDisease in loss of Ach receptors on skeletal m. Autoimmune. No depolarization -> no contraction
At rest axon terminal of motor nerve relases mini amount of AcH - miniature end plate potentials-Directly proportional to Ca2+-Inversely proportional to Mg2+
MUSCLES CHAPTER 12-13skeletal m. - striated, multinucleated.Stapedius m. smalles striated in bodygluteus maximus - most massivelatissimus dorsi - widestsartorius - longest-cells electrically isolated-hormone insensitive-40% body mass
cardiac m.single nucleusstriation, involuntary, intercalated discgapjuncitons
smooth m.single nucleus, non striated, involuntary, gapjuncitons-hormone sensitive
Contractility - ability to shorten with generation of forceExtensibility - stretching beyond normal lengthElasticity - ability to return to original resting length after stretch
Skeletal m.-Cannot contract without somatic motor neuron-their contraction is not directly influenced by hormones-flexors/extensors are antagonistic muscle groups
SarcoplasmSarcolemmaMyofibrils - one muscle fibers is like 100 myofibrilsSarcoplasmic retuculum SR - around each myofibrilT-tubules - allow AP to flow from surface to interior rapidly
Myosinhas light chains and heavy chains- motor domain and actin binding site—> Thick filaments
ActinG-actin to F-actineach G-actin has a myosin binding site—> Thin filaments
SarcomereZ-ZThin filaments attach to Z-discThick filaments to M-line
Muscle contraction-Force created by contraction - tension-Shrinks sarcomereContraction is the active creation of tensionLoad opposes contractionRelaxation is the release of tension
Titin - stabilizes myosin (TM)Nebulin - helps alligh actin (elli gick NA) - promotes strong acting-myosin interactions
Actin-myosin sliding-I band and H zone disappears shortening muscle-Myosin pulls on actin like a rope hailing - power strokes -Myosin ATPase provide energyCa2+ increases -> Ca bind to troponin-> troponin binds to tropomyosin that blocked actin binding sites on G-actin-> myosin can bind->power stroke
Relaxed state just before power stroke - 90 degree cross bridge
The rigor state - 45 degree cross bridge relative to filamentNo metabolism- no ATP-> muscles do not bind ATP -> rigor mortisthe tightly bound state
AcH released into synapse -> opening Na+ influx, K+ out -> end plate potential - Always above thresholdAP is conducted along T-tubules opening Na+ channelsAP in T-tubules alters DHP receptorDHPs open RyR Ca2+ release channels from SR->Ca2+ release from SRCa2+ binds to troponin allowing actin-myosin binding
DHP-RyR - electrochemical coupling. No extracellular Ca2+ needed
Note!In response to depolarization of T-tubule change of shape of DHPR is necessary for RyR activationwhile influx of Ca2+ is not
RelaxationCa2+ ATPase pumps Ca2+ back into lumen
one contraction-relaxation cycle - a twitchlatent period - between AP and muscle tension. Time for Ca2+ release and troponin binding
-Resting muscle stores ATP in phosphocreatine binds -fast intensive-=2 dependent fatty acid - used in light exercise-O2 dependent glycolytic - heavy exercise
Fatigue depends on not fast enough Ach synthesis and K+ release, an imbalance in membrane potential.
ATP needed for-Na+/K+ ATPase-Contraction (power stroke)-relaxation - active pumping of Ca2+ back to SR
Treppe effect-Graded response-In muscle rested for a prolonged period-Each contraction is stronger than previous until equal after a few stimuli
Slow twitch fibers -myoglobin rich red m. fiber.better blood supplyOxidative.Fatigue resistant.Smaller diameterFast twitch FOG IIA -large diameter- glycolytic rapid ATP split - contain myosin- white fibers, fewer and smaller mitochondriaFast twitch FG IIB - Pump Ca2+ faster. Fatigue most easily
Oxygen concentration is a factor - depend on myolglobin (has high O2 affinity)
FatiguePsychological - emotional stateMuscular - ATP depletionSynaptic - neuromuscular junction, lack of AcH
The tension a muscle can generate is directly proportional to number off cross bridges between thin and thick filaments - why optimal sarcomere length exists! Single twitch tension is determined by sarcomere lengthThen force generated by contraction can increase by increasing frequency at which APs stimulate muscle fibers
No time to relax completely -> summationUnfused tetanus - m. fibers partially relax - some Ca2+ can be recycled between contraction complete tetanus - no relaxation, flat line
Allo or none law for muscle fibers-Contraction of equal force in response to each individual AP when they arrive at sufficiently long intervalsGraded for whole musclesForce of contraction of whole muscle range from weak -> strong depending on stimulus strength.
Motor unit Somatic motor neuron + fibers it innervates(one fiber type only)more fine MU for e.g eye, bigger for like thighThere are fast twitch MU and slow twitch MU-Each alpha motor neuron innervates a motor unit-all cells in an MU contract simultaneously-small MU are recruited first(low threshold, size principle)
Graded force/contraction depending on-Changing types of active MU-And changing number of MU responding at any given timeDone by recruitmentWe are able to maintain constant tension due to variations in MU. The fatigued ones overlapped by pigga
->summation of force= function of stimulation rate
FINAL COMMON PATHWAY:Alpha motor neurons collecting inputs -> neuromusclular junction convergence of many neurons onto a single motor neuron
IsoTONIC contraction - creates force and moves loadSarcomeres shorten more but elastic elements are already stretched -> shortening of the muscle = concentricEccentric - tension maintained but muscle lengthens
Isometric contraction - force without moving load - staticCreates force but do not shorten, elastic elements.Sarcomeres still shorten(contract) but the elastic elements streches to maintain constant length-> Firm and ready for action at all times ->postural muscles of body
ATP for muscle contractionCreatine phosphate 3-15sekAnaerobic respiration 10sek-2min- glc -> ATP + lactic acidAerobic respiration - 38ATP/1 glc
Gravity produces tonic muscle tension
Smooth m.phasic- usually relaxedtonic - maintaining some level of tension - e.g sphincters
single unit smooth m. - linked by gap junctions -multi unit - cells not electrically linked, act independently - like iris/ ciliary m.
most smooth m. are single unit - visceral-actin myosin interaction-contracts by increase Ca2+ levels in cytosol-smooth m. relax and contract more slowly -require less ATP to generate and maintain force-no fatigue-no sarcomeres-single nucleated-higher sensitivity to ion conc. changes -tends to contract in response to sudden stretch(myogenic autoregulation of bloodflow)-amplutude of contraction constant - muscle length varies
Myosin phosphorylation controls contractionCa2+ binds to calmodulin-> phosphorylation of myosin light chain(kinase)Myosin ATPase -> contractionMLCP control Ca2+ sensitivityDense bodies
Autonomic control-Antagonistic control by sympathetic/parasympathetic-Bloodvessels(symp) and sphincters under tonic control-Linked to G-protein coupled receptors-Phospholipase C-> DAG relase of Ca2+ -> increase of MLCK and MLCP -> contraction-adenyl cyclase-> increase of cAMP -> increase of myosin phosphatase activity -> relaxation
Control of body movement and reflexessomatic reflexes - somatic motor neuronsautonomic reflexes - autonomic neuronsspinal reflexes - integrated in spinal cordcranial reflexes
Primitive reflexes/newbron - originate in brainstem, disappear in normal brain development. CP kids may retain theseInnate reflexes - born with it, may disappearLearned reflexesMonosynaptic reflex - A sensory afferent synapse direcly on a motor neuron. Only somatic motor reflexesPolysynaptic - at leas one interneuron, all autonomic reflexes, 1x afferent, 2x efferentSuperficial reflexes - stimuli of mucus/skin - corneal, cremasteric, suckling, plantarDeep reflexes - stretch reflexesSegmental - stretch reflexIntersegmental - flexion withdrawal - polysynaptic reflexessuprasegmental - swallowing
Most reflexes does not need to involve brain but brain can:Inhibit by increasing electronegativity (hyper polarize)Facilitate by decreasing electronegativity (depolarize)
The reflex arc - basic functional unit of our ns.
Autonomic reflexes-Visceral-Polysynaptic-could be spinal BUT modulated by excitatory/inhibitory signals from brain, like urination-Higher control of a spinal reflex - a learned response(?)-tonic activity
Skeletal m. reflexesMuscle info -> CNS -> Response:Contraction leas to activation of somatic motor neurons ORRelaxation - a result from absence of excitatory input by somatic motor neuron - they are inhibited
Proprioreceptors(sensory) - info of position and effort. Input to CNS via sensory neurons.CNS integrates via excitatory/inhibitory interneurons. Can become perception in cortex. Somatic motor neuron - carry output signal.Neurons innervating skeletal m. - called alpha motor neurons innervates extrafusal motor fibers
The 3 proprioreceptors1. Muscle spindle-stretch receptors -> causes stretch reflex - MYOTATIC REFLEX-paralell to extrafusal muscle fibers-each m. spindle in a capsule enclosing intrafusal m. fibers(lack myofilaments centrally, smaller and parallel to extrafusal fibers and can be stimulated by gamma motor neurons)-Has contractile ends but central region lacks myofibrils-Central region is excitable by 1. stretching of entire m. or 2. stretching of contractile ends(m. length remain constant!)-Innervated by gamma motor neuronsFunciton-reflex for muscle tone-transducers(sensors) of muscle stretch, amplitude and velocity)-indirect not voluntary initiator of m. contraction - patellar reflex
Gamma neuron stimulated ->The noncontrictile part is wrapped in sensory nerve endings -> info into sensory neurons -> spinal cord -> alpha motor neurons innervating that m.! Resting muscle has enough stretch to activate this tonic control -> muscle toneThis is also leads to reflex contraction to precent overstreching = stretch reflex.Stretch reflex maintains muscle tone and posture
! Prescence of gamma motor neurons keeps spindles active no matter length.Muscle contraction by alpha motor neurons while gamma MN keeps spindle tense at contractile end.Muscle spindle reflex: Putting a load in 90degree elbow hand - hand will fall and the set back into normal position due to muscle spindle.
Types of fibers within muscle spindle:
Type Ia - primary afferent fiber excited by both nuclear bag and chain fiber. 17mikrom in diameter-. Dynamic response to stress.short stretch.Excite alpha-mn via Monosynaptic pathwayhighest velocityType II - secondary afferent is only excited by chain fiber (thinner). 7mm.Static response to stress.Sustained stretch.mono and polysynaptic pathway
Both excite alpha motor neurons of that muscle Ia and II afferentes secrete glutamate
during motor activity both alpha and game motor neurons activated -> a-g coactivation
2. Golgi tendonJunction of tendon and muscle fiber-Active during isometric contraction(no load moved, force but do not shorten) hold a glass of water, yoga-Reflex Causes relaxation - prevent överansträngning-Free nerve endings inside CT capsule embedded in collagen fivers-Embedded in collagen fibers
Ib fibers - do not synapse directly on motor neuronsGTO much less sensitive to muscle stretch than stretch repectors - nerve endings are encapsulated
Muscle contraction tightens the fibers, squeezing nerve endings that fire afferents -> spinal cord-> inhibitory interneurons activation-> decreased excitatory output inalpha motor neuron->decreased contraction
This reflex slows muscle contraction an prevents over contraction !! Think back on holding the load in 90 degree angle, if the load becomes heavier then the tension the muscle can develop -> inhibition of alpha motor neurons-> relaxation and the arm falls.Important to protect the muscle fire from damage!
Deep tendon reflex-opposite of stretch reflex-activate GTO -> inhibitory interneuron -> decrease alpha neuron fire-stimulate contraction of antagonistic muscle(active & elasticity) ->contractive m. relaxes
Passive stretch of m.-spindle activated-> contraction of extrafusal m. fibers(stretch reflex)-not stretched enough for GTO
Active contraction- central activation of alpha MN-> contraction of extrafusal m. fibers-muscle spindle relaxed(inactivated)GTO activated - causes relaxation
Active contraction with gamma contraction-intrafusal and extrafusal fibers contract Ia and II afferents-GTO activated but inhibition too weak-when load becomes too great inhibition is strong enough and reverse mitotic reflex starts(muscle relaxation)
3.Movement around joints- diverging and converging pathways - myotatic unit-simplest reflex in myotatic unit - monosynaptic stretch reflex1- sensory neuron from spindle 2. alpha motor neuron to muscle
Knee jerk reflex1.monosynaptic stretch reflex of quadriceps - end of the stretch reflex is monosynaptic2. reciprocal inhibition(polysynaptic) of antagonist (hamstring)
1. Tap-> stretch-> spindle activation-> AP in sensory neuron->synapse in spinal cord-> efferent motor neuron->contraction of quadriceps — monosynaptic2.synapse in spinal cord also activate inhibitory interneuron -> synapse to inhibit motor neuron in hamstring(relaxation) —polysynaptic
Flexion reflexes - limb away from panful stimuli-Polysynaptic-Rely on divergent pathways in spinal cord-Takes longer time than spinal reflex-Both relaxation of antagonist and alpha motor neuron activation -> flexion
Noci(pain) receptor->affferent neuron->spinal cord->divergence:1.excitatory interneurons - alpha MN contraction -> flexion2.inhibitory interneursons to cause relaxation of antagonist
Flexor reflexes especially in e.g legs - accompanied by crossed extensor reflex:-Maintains balance when one foot is off the ground-> extensors contract in supporting leg, relax in flexed legOur natural gaair pattern, crawl, walk, run
MOVEMENT
Reflex movement-Least complex-Primarily spinal cord-Sensory input can reach brain for coordinationPostural reflex-Integrated in brainstem-Input from visual, vestibular and muscular proprioception-Reason for like blind seeing-Sensory feedback is used to refine reflex movement
Voluntary movement-Integrated in cerebral cortex-initiated without external stimuli-Can become reflexive-Muscle memory - developed when unconscious brain reproduce voluntary movements.
Rythmic movement-Walking/running-Combination of reflex/voluntary-Cerebral cortex initiates/terminates! Central pattern generators in-between— Animal paralyzed by spinal injury cannot initiate walk but if put on a treadmill CPGs will produce movement :)
! Maintnance of posture include all of the above mentioned movements
CNS integrates movementSpinal cord - integrates spinal reflexes and has CPGs - info from proprioreceptiosBrainstem/cerebellum - Central postural reflexes + hand/eye movement - info from proproiR(signals from vestibular apparatus co directly to cerebellum)Cerebral cortex/basal ggl - Voluntary movement
A pitcher decides ot throw a ballAP in interneurons of corticospinal tractMotor cortex -> spinal cord onto somatic MNContralaterall crossing in medullary pyramid (in pyramidal tract)->lateral corticospinal tract
Neurons from basal ganglia - extrapyramidal tractnoncrossing fibers - anterior corticospinal tract
ParkinssonProves basal ganglia has o role in body coordinationDisrupt in release of dopamine
Tetanus COntracted muscle paralysis by clostridium tetani.
Lecture CNS
-stimulus on free nerve endings -> graded potentials
Gray matter in CNS-cortex-nuclei-centers
White matter-tracts-columns - several tracts-Pathways - ascending and descending
PNS gray matter - gangliaPNS white matter - nerves
Divergence-broad distribution of specific input. pre and post
Convergence-several neurons synapse on same postsynaptic neuronsummation-> response
Serial processing neuron -> next neuronOne part of CNS to other
Parallell processingDivergence first then several neuronal pools process same information->many responses at the same time
Reverbeation1x neural pool/intermediate poolsends a positive feedback to keep chain of neurons active..Will continue into stimuli breaks/fatigue
Presynaptic inhibition3x target cellsOne has a inhibitory interneuron that synapses (hyper polarizing) -> no response in A->Response in B and C
Somatosensory pathway-Relayed ot brain/spinalcord via ascending pathways
Specific:1 typ of receptor1type of stimulusSpecific cortex areasNonspecificMore than one sensory unitTo brainstem, reticular formation, thalamus
FLowReceptor->1st order N(dorsal root ganglion)->2nd order N(spinal cord/brainstem)->3rd N(thalamus)->Somatosensory cortex(312)
Somatic part of sensory system transmit sensory information from skin, muscles, joints to CNS-all levels of spinal cord-reticullar formation, brainstem, midbrain-cerebellum,thalamus, somatosensory cortex
Receptors from dorsal rootPacinian corpuscle - vibration, pressure muchanoreceptorMuscle spindle, golgi tendon organEncapsulated endings! Free nerve endings form lateral division
Primary somatosensory cortex 312 postcentral gyrus parietal lobe+ sensory assosciation area
-ascending pathway in spinal cord - dorsal column (gracilis and cuneus)
Column in spinal cord - white matter (dorsal, ventral, lateral)Horn - gray matter (posterior, lateral, anterior)
Descenting tracts(motor)
Primary moter cortex, precentral gyrus € premotorcortex 6-> skeletal m. movement
Motor neurons in ventral horn of spinal cord
Direct pyramidal tract (corticospinal)-initiation on motor/premotor cortex-upper motor neuron motor cortex -> brainstem motor cortex -> spinal cord-lower motor neuron - alpha motor neuronsvoluntary movement and tone -only 3% Betz cells-80% cross at medullary pyramid -> lateral corticospinal tract-20% do not cross (eventually in spinal cord) -> anterior corticospinal tract. to postural muscles—most axons synapse with contralateral interneurons in spinal cord but some make monosynaptic connections to A/G motor neuronsBabinski respone -damage to corticospinal tract. Fanning of toes planter reflexCorticospinal - to muscles innervated by spinal motor neurons
Corticobulbar - motoroutput to muscles of face, tongue, throat
Indirect extrapyramidal tract-motor cortex-projections via brainstem nuclei-Neurons from basal ganglia - extrapyramidal tract-unconscious movemet - posture, balance-muccle toneRubrospinal tract - red nucleus. Flexors excitements, inhibit extensorzVestibulospinal tract - uncrossed bilateral - inc m. tone by gamma loop activation. no free fall while standing-Tectospinal tract - crossed-Terminates in spinal cord via interneurons which contact alpha and gamma motor neurons-Fibers which influence axial m. are crossed-Fibers for the limbs - mostly uncrossed->Permits independent control of the limbs and axial muscles.Manipulation can proceed while posture is maintained
Bell magendive lawAnterior/ventral spinal nerve roots = motorPosterior/dorsal nerve roots = sensory
The anterior spinal nerve roots contain only motor fibres and posterior roots only sensory fibres.
Stycknine poisoning - blocks inhibitory signals by competing with the inhibitory neurotransmitter glycine in spinal cord -> excitatory stateEasily activated muscles -> Muscle spasm. Death. In rat poising
glycine - inhibitory in spinal cordglutamate - excitatory
myotome same as dermatome but for motor output(muscle groups)
spinal schock - areflexiaearly - no stretch receptor, no sphincter tone, no sympathetic activity on smooth mlweeks - upper motor neuron signs develop, gradual reflex dec, some sphincter and ere tile, no voluntary control
Lessons from practice tests
Renshaw cells are inhibitory interneurons found in the gray matter of the spinal cord, and are associated in two ways with an alpha motor neuron.They receive an excitatory collateral from the alpha neuron's axon as they emerge from the motor root, and are thus "kept informed" of how vigorously that neuron is firing.They send an inhibitory axon to synapse with the cell body of the initial alpha neuron and/or an alpha motor neuron of the same motor pool.In this way, Renshaw cell inhibition represents a negative feedback mechanism. A Renshaw cell may be supplied by more than one alpha motor neuron collateral and it may synapse on multiple motor neurons.
-Renshaw cells act to inhibit sudden movements. Inhibit-inhibition af antagonistic muscle. -recurrent inhibition-control degree of efferent signal sent to the muscle -Descending cortical pathways modulate renshaw cells
Type 1a muscle fibers - in muscle spindle sensory. respond to change in length and velocitytype Ib in golgi tendontype II - fire when muscle is static
ATP is directly involved in relaxation of skeletal muscleActivation of renshaw cells -> increased permeability to Cl- ions and decreased AP in alpha motor neurons
The CSF has a lower glucose level than plasma
Alpha 2 motor neurons has low recruitment threshold - alpha 1 has high. Remember size principle - small motor unit and low threshold activated first.
Final motor pathway = alpha motor neuron and ad the end of that pathway we have: neuromuscular junction
Fast depolarization caused by voltage gates K+ channels ?
In monosynaptic spinal reflexestheir afferents and efferents are contained within same spinal nerve
the most used muscle fiber type in body areslow muscle fibers
flexion reflex involvesmore motor neurons than stretch reflex
activation of gamma motor neuronsstiumulates activation of alpha motor neurons
Inhibitorstetrodoxin(irriversible) - blocks Na+ channels - no APLidocaine(reversible) - blecks Na+ channels - no AP
Bartrachotoxin - opens Na+ channels irreversibly - blue froggy
Ach esterase breaks down acetylcholine to acetyl + cholineAch-esterase inhibitors ->spasm and hyperactivity of parasympathetic divisionIrreversible: flourophosphate, disopropylReversible neostygmine, phosphostygmine
Botulin - prevents release(exocytosis) of AchCurare - blocks the binding of Ach->no depolarizationStrychnine - inhibits glycine ”inhibits inhibition” -> excitation > uncontrolled convolusions and respiratory arrest. On frog on LABAtropne - blocks muscarinic receptors, inhibit parasympathetic neurons Ouabain - Na+/K+ ATPase inhibitor
! metroprolol - is B1 specific
neuron resting membrane potential = -70mVMuschle fiber resting membrane potential = -90mV
-Depolarization is not contraction!-ATP needed both for contraction and relaxation-Duration of AP in skeletal m. much shorter then duration of contraction - why summation is possible
https://www.dropbox.com/sh/7wd22woosu6ald2/AADtMrSAoLPmCyzXrAWhPy0Ya/physiology/Physio/PHYSIOTESTS/Physio/Tests%EF%80%A2Exams%205/PAT1/PAT1_-_summation.docx?dl=0
receptors sense a response via graded potentials
Somatotropic organization in ventral horn:
proximal muscles toward centerextensor most anteriorly
small MU - low threshold - activated firstslow MU fiber lower threshold
muscle tone cannot be voluntarily controlled
rubrospinal tract innervate flexor muscle - intact in decorticate but not decerebrate postion?
upper motor neuron damage - spastic, hyperreflexlower motor neuron - flaccid, no reflexes
Activation of renshaw cells-increased permeability of alphamMN to cl- ions
FALSElatency time of autonomic reflexes is the time needed for electromechanical coupling of ganglion cells
Skeletal m. has nicitinic cholinergic receptorsatropine block muscarinic
During normal movementred muscles fibers are recruited before white muscle fibers
In smooth m. increased levels of cAMP favors muscle relaxation
Labs
Human monosynaptic reflexes-Patellar-Achilles-Biceps and tricepsHuman polysynaptic-Flexion reflex-Abdominal reflex-Planter reflex(Babinski sign)
Propranolol test - proving parasympathetic influence on HRBeta blocker non selective
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