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Cell PhysiologyCell Membrane Structure and Components1. MOST abundant compontents are phospholipids and proteins Phospholipids hydrophilic head (glycerol) + hydrophobic tail (2 fatty acyl chains)form a BILAYER hydrophilic surface and hydrophobic interior
lipid soluble molecules dissolve through bilayer readily pass through bilayerwater soluble molecules will NOT dissolve through bilayer require channels
Proteins maybe intrinsic/integral or extrinsic/peripheral
Intrinsic / Integral Extrinsic / Peripheral
spans the ENTIRE membranelocated on ONLY 1 SIDE of themembrane (either internal or external)
attached via HYDROPHOBIC
interactions
attached via CHARGE
INTERACTIONS disrupted viadisrupted by DETERGENTS
disrupted by changing the IONICCOMPOSITION / pH of the medium
NOTE: membrane proteins are ASYMMETRIC domains outside and inside of cell are
DIFFERENTe.g. Na
+/K
+/ATPase and Ca2
+/ATPase pumps
2. Cholesterol stabilizes the cell membraneFLUIDITY BUFFER
3. Glycolipids and Glycoproteins function in cell-cell communication, and as receptorsand antigens
Glycolipids Glycoproteins
CHO bound to membrane LIPIDS CHO bound to membrane CHON
e.g. Receptor for Cholera Toxin (GM1)e.g. Fibronectin attachment to
extracellularmatrix
Fluid Mosaic Model some components CANNOTMOVE:
remain in 1 part of the cell membrane tethered by the cytoskeletone.g. anion exchanger in RBC tethered by ankyrin to spectrin
Ach receptors
DENERVATION SUPERSENSITIVITYif nerve to muscle is disrupted, Ach receptors spread throughout the musclemembrane sensitity to Ach
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some components CAN MOVE in the membrane:along the PLANE of membrane more rapid and spontaneousFLIP-FLOP between 2 monolayers less rapid, limited to small lipid-soluble molecules
Cellular Transport
PASSIVE TRANSPORTNO energy needed
ACTIVE TRANSPORTREQUIRES energy
SimpleDiffusion
FacilitatedDiffusion
Primary ActiveSecondaryActive
Endocytosis/Exocytosis
PassageTHROUGHmembrane?
YES YES YES YES NO
EnergyUSAGE? NONE NONE YES YES YES
What drivestransport?
random thermal motion ofparticles (Brownian motion)until concns are EQUAL
energy fromATP
energy from Na+
gradientenergy fromATP
CarrierMediated?
NO YES YES YES NO
Movement ofSolute
down gradientdowngradient
againstgradient
against gradient variable
Exampleswaterurea
ion channelsGlc transport
Na+/K
+/ATPase
Ca2+/ATPase
SYMPORT:Na
+/Glc and
Na+
/K+
/2Cl-
cotransport
ANTIPORT:Na
+/H
+, Na
+/C
2+
and Cl-/HCO3
-
exchange
LDL receptors
DiffusionDiffusion Coefficient (ABILITY to DIFFUSE)
r6KTD
Determinants of Diffusion Coefficient
1. KT: average kinetic energy of particles2. 6r: viscous drag during movement of particles
size of molecule (r): size : diffusion
3 MW
1r i.e. 8x MW is equivalent to only 2x )8(3 in diffusion
viscosity of medium (): viscosity : diffusion
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Ficks Law (RATE of DIFFUSION)
x
CDAJ
Determinants of Ficks Law
1. D: diffusion coefficient2. A: surface area for diffusion
3. C: concentration gradient ALWAYS compute C = (higher lower)4. x: thickness of membraneRULE OF THUMB:
x m in thickness x2 mS decrease in diffusion timee.g. 10 m increase in thickness = 100 ms (10
2) decrease in diffusion time
Summary of Factors that affect DiffusionINCREASES Diffusion DECREASES Diffusion
Lipid Solubilityoil:water partition coefficient HIGH LOW
Concentration Gradient HIGH LOW
Thickness of Membrane THINNER THICKER
Surface Area HIGH LOW
Size of Particles SMALL particles (low MW) BIG particles (high MW)
Temperature HIGH LOW
NOTES Can water-soluble substances move through membranes? through gaps between phospholipids if they are SMALL enough through water channels (aquaporins)
Osmosis simple diffusion of WATER through a SEMI-PERMEABLE membrane from LOW
SOLUTE to HIGH SOLUTE concentration
membrane must be permeable to water but NOT to solute if solute is permeable then it isNOT an effective osmole
Osmotic Pressure: HIGHER osmotic pressure : HIGHER water flow
)i(cRT Determinants of Osmosis1. c: MOLARITY2. R: gas constant (0.0821 L.atm/mol.K)3. T: temperature4. i: coefficient to determine EFFECTIVE osmoles (i.e. effectivity of
dissociation of ions)
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Osmolarity vs. TonicityOsmolarity Tonicity
refer to COMPUTED OSMOTIC PRESSUREcomputed via freezing point depression
HYPEROSMOLAR: GREATER
ISOSMOLAR: EQUAL
HYPOSMOLAR: SMALLER
refer to CONCENTRATIONS EFFECTON VOLUME
HYPERTONIC: causes SHRINKINGISOSMOLAR: NO EFFECTHYPOSMOLAR: causes SWELLING
refer to BOTH PERMEANT andIMPERMEANT solutes
refer ONLY to IMPERMEANT solutes
Notes: STEADY-STATE cell volume is determined ONLY by IMPERMEANT SOLUTES PERMEANT SOLUTES cause TRANSIENT effects only greater permeability, shorter
effect of transient changes
Reflection Coefficient reflects ease with which substance penetrates a membrane
Value is BETWEEN 1 and 0constant NEARER 1 IMPERMEABLEconstant NEARER 0 PERMEABLE
Properties of Carrier-Mediated Transport
1. FASTER than simple diffusion2. chemical SPECIFICITY include STEREOSPECIFITY e.g. L-Glucose not transported
3. SATURABLE: similar to Michaelis-Menten Kinetics in enzymes:
]S[K
]S[JJ
m
max
4. may be INHIBITED COMPETITIVE INHIBITION structural analogs ALLOSTERIC INHIBITION alters transporter affinity for substrate
METABOLIC INHIBITION inhibits Na+/K+/ATPase pump i Na+ gradient for 2oactive transport
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Ion Channels selective based on SIZE and CHARGE OF LINING
if POSITIVE charge: will repel cations, will allow anionsif NEGATIVE charge: will repel anions, will allow cations
conductance depends on PROBABILITY of opening or closingVOLTAGE-Gated regulated by membrane potentialsLIGAND-Gated regulated by chemical signals
Intercellular Connections attachments BETWEEN cells
Tight Junctions (Zonula Occludens) Gap Junctions
attachments WITHOUT a channel attachments WITH a channel
used for PARACELLULAR transport of
substances
renal distal tubule (tight/impermeable)renal proximal tubule (leaky/permeable)
used for INTERCELLULAR
COMMUNICATION
neurons (synapses)cardiac muscle
TRANSCELLULAR through the cell itselfPARACELLULAR in between cells, through tight junctions
Miscellaneous Na
+/K
+/ATPase usually BASOLATERALmaintains intracellular Na
+
2o
Active Transport uses Na+ gradient created by Na+/K
+/ATPase
Hence, inhibiting Na+/K
+/ATPase pump will indirectly inhibit 2
otransport mechanisms
Kinds of ATPases
P-Type V-Type F-Type
MOAuses aPhosphorylatedintermediate
accumulates H+
synthesizes ATP from H+
gradient
ExamplesNa
+/K
+/ATPase
Na2+/ ATPase
in lysosomes maintains acidicenvironmetn
in inner mitochondrialmembrane as part ofoxidative phosphorylation
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MEMBRANE POTENTIALSDIFFUSION / ELECTROCHEMICAL POTENTIAL potential difference (electrical potential) created by diffusion of an ion down its
concentration gradient (chemical potential) can be generated ONLY by PERMEANT
ions
MAGNITUDE depends on CONCENTRATION GRADIENTSIGN depends on CHARGE OF DIFFUSING ION and DIRECTION OF
MOVEMENT
net movement of ions depends on which is larger(potential difference vs. concn gradient)
EQUILIBRIUM POTENTIAL a KIND of DIFFUSION POTENTIAL
diffusion potential where electrical potential is EQUAL AND OPPOSITE TO chemicalpotential leading to NO NET MOVEMENT OF IONS!
Nernst Equation: used to calculate for the EQUILIBRIUM potential of a particular ion
extra
raint
]A[
]A[ln
zF
RTE
Determinants of E1. [A]: concentration of ions
2.F
RT: constant that depends on TEMP (~60 mV at 37
oC)
3. z:CHARGE of the ion
NOTES: the equilibrium potential DIFFERS per ION CHARGE of the potential refers to charge RELATIVE TO INTRACELLULAR compartment:
if E is NEGATIVE INTRACELLULAR more () if E is POSTIVE INTRACELLULAR more (+)
Relationships in the Nernst Equation
EEqand MEASURED Ehave the SAME sign
EEq> MEASURED Eelectrical and chemicalpotential OPPOSING, BUTelectrical > concentration
EEq< MEASURED Eelectrical and chemicalpotential OPPOSING, BUTelectrical < concentration
EEqand MEASURED E have OPPOSITE signs electrical and chemicalpotential SAME direction
VERY FEW ions are needed to achieve equilibrium
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RESTING MEMBRANE POTENTIAL from the contributions of the equilibrium potentials of ALL permeant ions
Equilibrium Potentials
ENa = + 65 mVECa = + 120 mV
Resting
MembranePotential(~ -70 mV)
Impermeant Ions (~ -
10Mm) phosphates, proteins, nucleic acids
EK = - 85 mV
ECl = - 85 mV
K+
has the GREATESTPERMEABILITYresting potential isNEAREST the E of K
+
Na/K/ATPasePump (~ -5 mV)
electrogenicpump
Gibbs-DonnanEquilibrium
steady-state if BOTHpermeant andimpermeant ions arepresent
NOTES: Resting Membrane Potential is from contribution of:
1. Individual equilibrium potentials ofALL permeant ions MAJOR contributor
CHORD CONDUCTANCE EQUATION: membrane potential is the weighted averageof all equilibrium potentials (only the PERMEANT ions)
2. Na/K/ATPase Pump MINOR contributor (~ -5 mV)
3. Negative Intracellular Substances (Gibbs-Donnan Equilibrium) MINOR contributor (~ -10 mV)
DIGITALIS
the cardiac Na/K/ATPase Na+
accumulates intracellularly with activity of Na/Caexchanger in CELL MEMBRANE Ca
2+sequestered by SR which leads to Ca
2+
released during contraction GREATER CARDIAC CONTRACTION
HYPERKALEMIA and HYPOKALEMIA
HYPERkalemia: outward currentDEPOLARIZES membraneHYPOkalemia: outward current HYPERPOLARIZES membrane
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ACTION POTENTIAL RAPID DEPOLARIZATION followed by SLOWER REPOLARIZATION
Depolarization
potential becomes LESS NEGATIVE (or MOREPOSITIVE)
caused by INWARDCURRENT of Na+
Threshold Potential LEVEL of membrane potential at which action
potential becomes INEVITABLE i.e. there will be anaction potential FOR SURE
Action Potential (Upstroke)
UpstrokerapidINWARDcurrent of Na+
opening of Na+
activation gatesOvershoot
peak of actionpotentialmembranepotential is POSITIVE
Repolarization/ Recovery
slow OUTWARDcurrent of K
+
closing of Na+INactivation gates
opening of K+
channels
closing of Na+ inactivation andopening of K+ are both SLOWERthan activation
Repolarization (Recovery) potential slowly returns to membrane potential
caused by OUTWARDCURRENT of K
+
Undershoot (Hyperpolarizing Afterpotential) potential MORE NEGATIVE than resting
K+
conductance remainshigher than at rest
Properties of Action Potentials1. stereotypical shapeSAME shape throughout length of nerve or muscle
2. self-propagating the action will spontaneously propagate from the site ofcreation
3. all-or none there is no INTERMEDIATE level of action potential4. voltage inactivated persistent depolarization INACTIVATES Na
+channels
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Comparison of Action Potential in different tissues:Nerve andSKELETAL Msc
CARDIAC Msc SMOOTH Msc
ShapeSTEEP
depolarization
STEEP depolarization
then PLATEAU
GRADUAL
depolarization
Cause ofOvershoot
opening ofFAST Na
+ opening ofFAST Na+ and SLOWL-Type Ca
2+
opening ofSLOW L-Type Ca
2+
Cause ofRecovery
closure of FASTNa
+
opening of K+
closure of FAST Na+
and SLOW L-Type Ca2+
opening of K+
closure SLOW L-Type Ca
2+
opening of K+
REFRACTORY PERIODS
ABSOLUTE REFRACTORY PERIOD RELATIVE REFRACTORY PERIODWHOLE of depolarization + FIRST1/3 ofrepolarization
REMAINING 2/3 of repolarization onwards
NO action potential will be generated action potential CAN be generated NEEDS GREATER inward current (greaterstimulus)
ALL Na+
channels closed SOME Na+
channels ALREADY OPEN,BUTK
+conductance is GREATER
ACCOMODATION cell membrane SLOWLY and GRADUALLYdepolarized action potential NOT generated
even if ABOVE threshold potential- voltage-gated Na+ channels become deactivated and the REQUIRED CRITICAL
NUMBER of Na+ channels for depolarization will never be reached
Propagation of Action Potentials through spread of local currents that DEPOLARIZES ADJACENT MEMBRANE if
threshold is reached, a NEW action potential will be created
Action Potential Local Response
LARGER changes in potential SMALLER changes in potential
CONSTANT shape CHANGING shapemagnitude REMAINS CONSTANT evenwith increasing distance
magnitude DECREASES with increasingdistance
SALTATORY conduction ELECTROTONIC conduction
LOCAL RESPONSE refers to the spread of depolarization using LOCAL CURRENTS
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Properties of Action Potential propagation:1. MAINTAINS THE SAME SHAPE: FREQUENCY OF ACTION POTENTIALS (rather than
magnitude) is used to transmit information (think Morse Code)
2. UNIDIRECTIONAL: ONLY forward because the previous membrane is still in itsABSOLUTE REFRACTORY PERIOD
3. SALTATORY: action potential generated only at NODES OF RANVIER (myelininsulates the membrane) action potential JUMPS from 1 node to the next
Speed of Propagation
1. diameter : speed due to resistance2. myelinatin : speed due to length constant
capacitancerestricting generation to nodes
SYNAPTIC AND NEUROMUSCULAR TRANSMISSIONElectrical Synapse Chemical Synapse
Mechanismgap junctions(6 connexIN = 1 connexON)
neurotransmitters
Speed ofTransmission
rapid (no delay)slower (with synaptic delay)mainly from neurotransmitterrelease
Direction of
Transmission
Bidirectional
(if unidirectional = rectification)
UNIdirectional(from pre- to post-synaptic
neuron only)
Where found
hepatocytesmyocardiumintestinal smooth muscleepithelial cells of lens
CNS and PNS
INPUT-OUTPUT RELATIONSInput action potential in PRE-synaptic cellOutput action potential in POST-synaptic cell
One-to-One neuromuscular junction no integration
One-to-Many Renshaw Cells in cord inhibition of motor neuronMany-to-One motor neurons with integration
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Pre-
Synaptic
DEPOLARIZATION of PREsynaptic Neuron Active Zones: areas of pre-synaptic membrane with thesynaptic vesicles
1. opening of voltage-gated Ca+
channels entry of Ca
2+into pre-synaptic terminal
2. neurotransmitter released from pre-
synaptic neuron via exocytosis
Post-Synaptic
NEUROTRANSMITTER IN SYNAPSE
diffuses through the synapse to reach thepost-synaptic neuron (or muscle end-plate)
ACh receptors concentrated atlips of junctional fold
Nerve: Post-Synaptic Potential (PSP)Muscle: End Plate Potential (EPP) From other neurons
EPP and PSP are only LOCAL RESPONSESand are NOT action potentials
PSPEPP
PSPEPP
PSPEPP
PSPEPP
SUMMATION (Spatial and Temporal) THRESHOLD
GENERATION and PROPAGATION of ACTION POTENTIAL
NOTES:
Acetyl CoA +Choline
Ach Acetyl CoA +Choline
Choline
Acetyltransferase
Acetylcholinesterase
- found in the cellmembrane of muscle
Choline: NOT actively synthesized reuptake from ECF (Na+-choline co-transport)
END PLATE POTENTIAL: release of ACh caused by DEPOLARIZATIONMINIATURE END PLATE POTENTIAL: SPONTANEOUS and RANDOM release of ACh
post-synaptic cell membrane does NOT generate action potentials EPP (local responsesonly) spread electrotonically to AXON HILLOCK and INITIAL SEGMENT
AXON HILLOCK part of neuron where axon originatesINITIAL SEGMENT first part of the axon
Lambert-Eaton Myasthenic Syndrome: antibodies vs. Ca2+
channel no release of Ca2+
Myasthenia Gravis: antibodies vs. ACh receptor no stimulation of muscle
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EPSP vs. IPSP types of POST-SYNAPTIC POTENTIALS maybe EXCITATORY or INHIBITORY
EXCITATORY (EPSP) INHIBITORY (IPSP)What it does tothe post-synapticneuron
DEPOLARIZATIONto generation of AP
HYPERPOLARIZATIONto generation of AP
Mechanism
opens Na+
channelsopens K
+channels
- brings membrane potentialhalfway between ENa andEK past threshold
opens Cl-channels
opens K+
channels
- Cl-has a MORE NEGATIVE
E than K+
NeurotransmitterExamples
- GlutamateMAJORexcitatory neurotransmitter
in brain- Acetylcholine (ACh)- Norepinephrine (NE)- Epinephrine (Epi)- Dopamine- Serotonine (5-HT)
- -Aminobutyric Acid(GABA)MAJOR
inhibitory neurotransmitter- Glycine
Types of Summation Summationadditive effect of smaller AP to produce a larger AP
SPATIAL inputs reach post-synaptic neuron AT THE SAME TIMETEMPORAL inputs reach post-synaptic neuron ONE AFTER THE OTHER
Facilitation, Augmentation, Post-Tetanic Stimulation
FacilitationPost-TetanicPotentiation
Long-Term Potentiation
Pre-SynapticREPEATEDstimulation
TETANICstimulation
REPEATED stimulation
Post-Synaptic greater greater Greater
DurationSHORTESTmilliseconds
INTERMEDIATEsecs to minutes
LONGESTdays to weeks
MechanismPRE-SYNAPTIC NEURON neurotransmitter release (2
oto
pre-synaptic Ca2+
)
PRE-SYNAPTIC NEURON neurotransmitter release
POST-SYNAPTIC NEURON sensitivity to neurotransmitter(2
oto NMDA receptor and in
post-synaptic Ca2+
)
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CRITERIA FOR NEUROTRANSMITTERS1. pre-synaptic neuron must produce and store the neurotransmitter2. neurotransmitter must be released by pre-synaptic neuron when stimulated3. application of neurotransmitter to post-synaptic neuron must have the same response as
when stimulating the pre-synaptic neuron4. application of neurotransmitter and pre-synaptic stimulation should be altered the same way
by drugs
Kinds of neurotransmittersNeurotransmitter Precursor Degradation
AcetylcholineAcetyl CoA + CholineCholine Acetyltransferase
Breakdown:Acetylcholinesterase
Reuptake:choline to pre-synaptic neuron
Norepinephrine Tyrosine
L-dopaTyr Hydroxylase
L-Dopa DopaDopa Decarboxylase
Dopa NorepinephrineDopa- -HydroxylaseNorepinephrine EpinephrinePhenylethanolamine-N-
Methyltransferase
Breakdown:Monoamine OxidaseCatechol-O-Methyltransferase
Reuptake:catecholamine to pre-synapticneuron
Epinephrine
Dopamine
Serotonin Tryptophan 5-HT
Histamine Histidine Histamine
Glutamate Glutamate
normal AA metabolismGABAGlutamate GABAGlutamate Decarboxylase
Glycine Glycine
Peptide vs. Non-Peptide NeurotransmittersNON-Peptide Peptide
Producedin nerve terminal as activesubstance
in nerve body (transported by fastaxonal transport) as prehormone
Mechanism small and clear large and electron-dense
Release into the synapse near cell body
Degradation reuptake into pre-synaptic neuron proteolysis of peptide
Duration short latency, short duration long latency, long duration
ExamplesAch, NE, Epi, Dopa, 5-HT VIP, opioids, CCK, Substance P,
TRH
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Notes: Fast Axonal Transport
Kinesin to nerve terminalDynein to nerve body
OpiATE SHOULD be produced from the oppy seed OpiOID NOT produced from poppy but with same effects
Neurotransmitter Release from Pre-Synaptic Neuron: via exocytosisV-SNARE in Vesicle membrane synaptobreVinT-SNARE in Terminal membrane synTaxin and SNAP-25
EXTRACELLULAR REGULATIONEndocrine Neurocrine Paracrine Autocrine
Produced byendocrineglands nerves
DIFFERENTcell type
SAME celltype
Effectdistant (viablood)
local (by diffusion)
Types of Signal Transduction PathwaysIonotropicReceptors
Ionotropic Receptor receptor is an ionchannel
Metabotropic Ion Channel 2n
messenger activates ion channel
SecondMessengers
5 Common Kinds of Second Messengers
cAMPAdenylateCyclase
Protein Kinase A(A for cAMP)
cGMP GuanylateCyclase
Protein Kinase G(G for cGMP)
ITP andDAG
Phospholipase C
ITP: Ca+
in cell(from ER (SR in msc))
DAG: Protein Kinase C
Ca2+
Ca
+ONLY: Ca
+-Calmodulin Protein Kinase
Ca2+
+ DAG: Protein Kinase C (C for Ca2+
)
Tyrosine
Kinases
Receptor Kinase receptor itself is the kinase
Receptor-AssociatedKinase
receptor activates another kinase through theJAK-STAT Pathway (Janus Tyrosine Kinases(JAK) and Signal Transducers and Activators ofTranscription (STAT))
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G-Proteins mediator / interface between second messenger and receptor HETEROTRIMERIC: composed of 3 different subunitsONLY active (A for Active) bound to GTP (has INTRINSIC GTPase activity)
inactive bound to GDPG Protein Effector Hormones/NT
GS (S forStimulate)
MAIN: stimulateAdenylate Cylcase cAMP NE (1,2)and EpiHistamineGlucagonACTH/FSH/LH/TSH
OTHERS: increase Ca2+
influx
Gi (I for Inhibit)Gi1, Gi2, Gi3
MAIN: inhibitAdenylate Cyclase cAMPNE (2 adrenergic)Ach (Muscarinic)OpiatesAngiotensinProstaglandins
OTHERS: activate Phospholipase C and A2 (A2 for
Prostaglandin Synthesis) open K+ channels (MUSCARINIC ACh)
Gt (T is forTransducin)
stimulatecGMP Phosphodiesterase cGMPT1: rodsT2: cones
Golf (OLFaction) stimulateAdenylate Cylcase cAMP different odorants
Gq stimulatePhospholipase C ITP, DAG and Ca2+
Ach (Muscarinic)
NE (1 adrenergic)
CHOLERA
binds to subunit of Gs permanent activation of adenylate cyclase and cAMP opening of Cl
-channel in intestines and WATER LOSS
Down-Regulation and DesensitizationDown-Regulation number of receptors via internalization of receptorsDesensitization sensitivity of receptors via phosphorylation (e.g. -arrestin in b-
adrenergic receptors)
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Kinds of neurotransmittersNeurotransmitters MOA Receptors Where found?
Acetylcholine open Na+ and K+
channels (Na+
> K+)
muscarinicnicotinic
Neuromuscular JunctionALL PRE-ganglionic
POST-ganglionicPARAsympatheticBasal GangliaBetz Cells (Motor Cortex)
C
atecholamine
Norepinephrine varies- and -adrenergic
POST-ganglionic SYMPAthetic
Epinephrine cAMP
Adrenal Medulla (ChromaffinCells)
DopamineD1: Gs, cAMP
D2: Gi, cAMP
D1D2
hypothalamussubstantia nigra
ventral tegmentum
BiogenicAmine
Serotoninbrain stempineal gland (converted tomelatonin)
Histamine hypothalamus
AminoAcids
GlutamateAspartate
AMPA (quisqualate receptor):open Na+ and K+ channels GluIS THEMAJOR
EXCITATORYNEUROTRANSMITTER
throughout the CNS
NMDA: open Ca+, Na
+and K
+
channels
Kainate: similar to AMPA
L-AP4: pre-synatic inhibitor
Metabotropic: IP3 and Ca+
GABA
GABA A:opens Cl
-channels
GABA B: opens K+
channels
GABA AGABA B
MOST COMMONNEUROTRANSMITTER IN THEBRAIN (1/3 of synapses)
basal ganglia
cerebellar Purkinje cellsspinal interneurons
Glycine opens Cl-channels spinal interneurons
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Kinds of neurotransmittersNeurotransmitters MOA Receptors Where found?
Neuropeptides
OpioidsEnkephalinEndorphins
Dynorphine
Endorphin: CNS (pain perceptionpathways)
Enkephalin and Dynorphin:everywhere else
Non-OpioidsSubstance PVIP, Secretin andCCKGlucagonNeurotensin
Substance P: NT of primarysensory neurons
VIP: smooth muscle, glands
CCK: GB contraction
Neurotensin: lowers body temp
PHYSIOLOGY OF THE NERVOUS SYSTEMNeuroglia and their FunctionsNeuroglianeural glue; supportive cells MORE NUMEROUS than neurons (10
13vs. 10
12)
Neuroglia Function
CNS
Astrocytes contribute to blood-brain barrier via foot processes buffer the extracellular environment of neurons forms scars after neural injury
Oligodendroglia form the myelin sheath in the CNS
Microglia phagocytes of the CNS
Ependymal
Cells
epithelium that separates CNS from CSF
produce CSF via choroid plexus
PNS
Schwann Cells form the myelin sheath in the PNS analogous to oligodendroglia in CNS
Satellite Cells cover dorsal root and CN ganglia analogous to astrocytes in CNS
Axonal Transportprovide movement of substances from soma to the axons
FAST Axonal Transport SLOW Axonal Transport
for membrane-bound proteins or organelles for dissolved proteinsFAST: 400 mm/day SLOW: 1 mm/day
ANTEROgrade Axonal Transport from soma to axon via KinesinRETROgrade Axonal Transport from axon to soma via Dynein
Herpes Zoster (Shingles): anterograde transportTetanus Toxin: retrograde transport
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Nervous Tissues Reactions to InjuryDegeneration Regeneration
CHROMATOLYSIS: to NEURON change in staining of the soma 2
oto
protein synthesis staining withbasic aniline dyes
cell swelling eccentric location of nucleus
WALLERIAN DEGENERN: to AXON disintegration of axon DISTAL to
transaction phagocytosis of myelin (EXCEPT
Schwann Cells (PNS) remain viable)
follows the path of Schwann Cells limited by slow axonal transport
ABSENT IN CNSbecauseoligodendrogliadoNOTform a path that growth sprouts cangrow into.
Autonomic Nervous System ALWAYS efferent (i.e. NO SENSORY COMPONENT)
Sympathetic Parasympathetic Somatic
PREganglionicNerve
THORACOLUMBAR Lateral Horn of T1-
12, L1-L3
SHORT nerve
CRANIOSACRAL CN X, IX, VII, III (1973) S2-S4
LONG nerve
NT between PREand POSTganglionic
NICOTINIC AChfor the WHOLE ANS
Autonomic GangliaParavertebral
Sympathetic Trunksnear effector organ
POSTganglionicNerve
LONG nerve (farfrom effector)
SHORT nerve (alreadynear effector)
NT betweenPOSTganglionic andEFFECTOR
NE (ALL and )
MUSCARINIC AChONLY for sweating
MUSCARINIC ACh NICOTINIC
Ach
Effector OrgansSMOOTH and CARDIAC muscleglands
SKELETALmuscle
NOTES: Autonomic Ganglia: refer ONLY to the cell bodies of the POST-synaptic neurons
Adrenal Medulla has NOPOST-ganglionic neurons direct stimulation from PRE-ganglionic neurons (NICOTINIC ACh)EPI 80%NE 20%
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Autonomic NS Receptor Types1 2 1 2
Main Action EXCITE (contractand constrict)
INHIBIT(dilate and relax)
EXCITE (contractand constrict)
INHIBIT(dilate and relax)
Mechanism ITP and Ca + cAMP cAMPWhere found and Actions
Blood Vesselsskin and viscera
VASOCONSTRICT
skeletal muscle
VASODILATE
SphinctersGIT and bladder
CONSTRICT
Smooth Muscle
GIT
MOTILITY SECRETION
GIT, UB and Lungs
RELAX / DILATE
Heart
Myocardium andSA/AV Nodes
HR, contractionand conduction
Other Locations and Actions
Iris
Radial Muscle
PUPILLARYDILATE
MALE GenitalsPresent
EJACULATION
KidneysPresent
RENINFat Cells
Present
LIPOLYSISNOTES: PARAsympathetic is just the OPPOSITE of everything above MUSCARINIC ACh
Nicotinic Muscarinic
ALL post-ganglionic neuronsSKELETAL muscle
(RECALL:ACh is NTbetweenpre- andpost-ganglionic neurons post-ganglionicneurons must have receptors for ACh)
SMOOTH and CARDIAC muscleglands
ALWAYS excitatory EXCITATORY: smooth msc and glandsINHIBITORY: heart
IONOTROPIC receptor EXCITATORY: ITP and Ca+
INHIBITORY: cAMP open of K+
chan.
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SWEATING IS SYMPATHETIC BUT MEDIATED BY MUSCARINIC ACh!
AUTONOMIC CENTERS IN BRAIN
Medulla
vasomotor center
breathing center controls RRswallowing, coughing, vomiting centers
Ponspneumotaxic center controls depth ofbreathing
Midbrain micturition center
Hypothalamusthirst and hunger centerstemperature center
SENSORY NERVOUS SYSTEM
Sensory Receptors transducer environmental signal to action potentialReceptive Field area of body that changes the firing rate of a sensory
neuron when stimulated
Classification of Sensory ReceptorsSpecial Superficial Deep Visceral
VisionAuditionOlfactionTaste
Balance
TouchPressureVibrationTemperature
Pain
DEEP pressureDEEP painProprioception
DistentionHungerVisceral Pain
Kinds of Nerve FibersGENERALFiber
MOTOR fibersSENSORY Fiber Myelination Diameter Velocity
A : motoneuronsto muscle
Ia: muscle spindleMyelinated Largest Fastest
Ib: Golgi tendon organ
II: muscle spindle
Myelinated Medium Medium: vibration (Paccinian) andtouch
: motoneuronsto spindles Myelinated Medium Medium III: pressure and pain
Myelinated Small Medium: touch, FAST pain andtemp
B PREganglionic autonomic Myelinated Small Medium
C IV:SLOW pain and tempNOTmyelinated
Smallest Slowest
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Adaptation of Sensory ReceptorsSlowly Adapting Rapidly Adapting
a.k.a. tonic phasic (PHAS forFASt)
StimuliDetected
respond to prolonged stimulirespond to changes in firingfrequency
STEADY stimuli CHANGING stimuli (on-off)
ExamplesPressure (Ruffinis Corpuscle)SLOW Pain
vibration (Paccinian Corpuscle)light touch
Steps in Sensory TransductionNeuron Locn of Cell Body
1st
ORDERDorsal RootCord Ganglia
sensory receptor receives stimulus
receptors may be epithelial cells or primary afferentneurons
ion channels opened DEPOLARIZATION(Receptor/Generator Potential) of sensory receptor
EXCEPTIONSare the rods and cones which areHYPERPOLARIZED
threshold potential reached action potential
generated
2nd
ORDERSpinal CordBrainstem
AP transmitted to 2nd
order neurons
3rd
ORDER Thalamusthalamus receives ALL sensory input for relaying tothe cortex
4th
ORDERSensory Cortex(Parietal)
conscious perception of stimulus
NOTES: CROSSING OVER at level of 2
NDORDER NEURON
THRESHOLD STIMULUS: WEAKEST stimulus that can be reliably detected
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SOMATOSENSORY SYSTEMPathways of Touch, Movement, Temp and Pain
Dorsal Column Spinothalamic (Anterolateral)
Modalities
FINE touchPressureVibrationProprioception2-Point Discrimination
LIGHT touchPainTemperature
Receptors
Paccinian vibration phasic
FREE NERVE ENDINGSMeissner flutter phasic
Ruffinis pressure tonic
Merkels Disc location tonic
Nerve TypesGroup A- fibers myelinated, large diameter fast
conduction
Group III (Group A-) fibers myelinated, medium diameter
FAST conduction
Group IV (Group C) fibers unmyelinated, small diameter
SLOW conduction
1st
OrderNeuron
DORSAL ROOT GANGLIONtravels up the Dorsal Funiculus of thespinal cord to medulla
PRIMARY AFFERENT FIBERSsynapses at the SPINAL CORDalready
2
nd
OrderNeuron
Medulla
Nucleus Cuneatus and NucleusGracilisMedial Lemniscus tothalamus
ANTEROLATERAL SPINAL CORD
ascends to the ventral part of LateralFuniculus to thalamus
3rd
OrderNeuron
THALAMUS1. CORD: Ventral Posterior Lateral
(VPL) nucleus
THALAMUS1. Ventral Posterior Lateral (VPL)
nucleus2. Intralaminar Complex
4th
OrderNeuron
SOMATOSENSORY CORTEXSI: PRIMARY Somatosensory Cortex post-central gyrusSII: SECONDARY Somatosensory Cortex superior bank of lateral fissure
NOTE:forSpinothalamic Pathway:projection toCingulate GyrusandInsula(Limbic System)
NOTES: SUBSTANCE P: neurotransmitter for pain
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Comparison of Cutaneous Receptors
Paccinian Meissner Ruffini Merkel
Adaptation Phasic Tonic
Modality vibration velocity pressure locationStructure /Location
onion-shaped,subcutaneous
in GLABROUS(non-hairy) skin
encapsulatedin epithelialcells
ReceptiveField
HIGH frequencyarea
LOW frequencypunctate
stretching punctuate
AXON REFLEXANTIDROMAL spread of action potential (towards site of stimulus) release ofSUBSTANCE P and CALCITONIN-GENE RELATED PEPTIDE (CGRP) inflammation
Somatosensory Homunculus
LOWER EXTREMITY medial surfaceUPPER EXTREMITY dorsolateral surfaceFACE above lateral fissureHEAD upper and lower extremityABDOMINAL superior banks of lateral fissure
NOTE difference between HEAD and FACE
FACE: Trigeminal Nerve
1st
Order NeuronPrimary Afferent Neuron travels through CN V to the trigeminal ganglion
2nd
Order Neuron
Trigeminal Ganglion
travels through the Trigeminothalamic Tract to thethalamus
3rd
Order NeuronThalamus Ventral Posterior MEDIAL (VPM) Nucleus
4 Order Neuron Somatosensory Cortex
Effects of Pathway Interruptions
Dorsal Cord Graphesthesia and Astereognosia in IPSILATERAL side
Ventral CordSensory and Affective components of Pain inCONTRALATERAL side
VPL and VPM
Nuclei
ALL sensation from CONTRALATERAL side of body
EXCEPT AFFECTIVE component of painSomatosensoryCortex
ALL sensation from CONTRALATERAL side of body,following the homunculus
ParietalAssociationCortex
CONTRALATERAL findings of the ff:1. neglect2. constructional apraxia3. dressing apraxia
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SPECIAL SENSESTEN Layers of the Retina
Pigment CellsPigmentedRetinal Layer
11-cis-retinalall-trans-retinal via LIGHT(photoisomerization) Metarhodopsin II
VITAMIN A: necessary for regenerationof 11-cis-retinal
Rods and ConesPhotoreceptorLayer
1. Metarhodopsin II Gt (transducin)T1: rods; T2: cones
2. cGMP Phosphodiesterase cGMP3. CLOSURE of Na
+channels
4. HYPERPOLARIZATIONneurotransmitter release
External LimitingMembrane
NUCLEI of rods/conesOuter NuclearLayer
AXONS of Rods/Cones +AXONS of Bipolar Cells
Horizontal Cells
Outer PlexiformLayer
NUCLEI of Bipolar CellsInner NuclearLayer
If NT from rods/cones is:- Excitatory:HYPERpolarization of bipolar- Inhibitory:DEpolarization of bipolar
AXONS of Bipolar Cells +AXONS of Ganglion Cells
Amacrine Cells
Innter PlexiformLayer
1. CENTER of receptive field: receptor toganglion DIRECTLY
2. SURROUND of receptive field: receptorto ganglion via HORIZONTAL CELLS
- usually ON-CENTER, OFF-SURROUND
NUCLEI of Ganglion CellsGanglion CellLayer
OUTPUT cells of the retina
AXONS of Ganglion CellsOptic NerveLayer
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Internal LimitingMembrane
Projections of Mller Cells
Optic PathwaysComposed of: LESION
Optic Nerve L and R Optic NervesMONOCULARblindness, NOmacular sparing
Optic Chiasm crossover of L and R NASAL retinaBitemporalHemianopsia
Optic TractRIGHT from R TEMPORAL + L NASAL
CONTRALATERAL Homonymous
Hemianopsia
LEFT from L TEMPORAL + R NASAL
LATERAL Geniculate Body(analogoustothalamus
RIGHT from R Optic Tract
LEFT from L Optic Tract
Geniculocalcarine Tract(Optic Radiation)
Temporal(Meyers Loop)
LOWER hemiretinaCONTRALATERAL HomonymousHemianopsia, WITHmacular sparing
Parietal UPPER hemiretina
Visual Cortex
(Layer 4 of Striate Cortex)
banks of the CALCARINE FISSURE CONTRALATERAL Homonymous
Hemi- orQuadrantanopsia,WITHsparing
LINGUAL GYRUS
ventral to fissure
LOWER hemiretina
CUNEUSdorsal to fissure
UPPER hemiretina
NOTES: Rods vs. Cones
Rods Cones
G-Protein T1 T2
Synapse with Bipolar MANY-to-one FEW-to-one
Amount of photopigment MANY LESS
Acuity low high
Sensitivity High lowLight Adaptationreduction in rhodopsin
worse better
Night Adaptationregeneration of rhodopsin
adapts LATER adapts EARLY
Day or Night? NIGHT vision (scotopic) DAY vision (photopic)
Presence in Fovea absent present (for acuity)
Color Vision NO YES
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Cells in the Visual CortexSIMPLE bars of light with correct orientation and positionCOMPLEX MOVING bars of lightHYPERCOMPLEX curves and angles
Chemical Reactions of VisionLIGHT
opsin + 11-cis-retinal rhodopsin all-trans-retinal + opsin retinol
PURPLE WHITEopsin released afterisomerisation to all-trans retinal
COLOR VISION:Trichromacy Theory
- absorption best at RED, GREEN and BLUE (RGB) color results from differentcombinations of RGB
- color results from differences in WAVELENGTH, but NOT in INTENSITY
TRICHROMAT ALL 3 colors PRESENT, NORMALMONOCHROMAT ALL 3 colors ABSENT
DICHROMAT ONLY 2 colors present, loss of 1 colorProtanopia loss of red (longest )
Deuteranopia loss of green (medium)
Tritanopia loss of blue (shortest )
Pupillary Light Reflex
Retina Pretectum EDINGER-WESTPHAL NUCLEUS dilator
Interconnectionbetween L & R
PARAsympathetic
Direct Reflex ipsilateral eyeConsensual Reflex contralateral eye
Errors of RefractionEmmetropia NORMALHypertropia far-sighted, focus BEHIND retina correct with CONVEX lens
Myopia near-sighted, focus IN FRONT of retina correct with CONCAVE lensPresbyopia loss of accommodation correct with CONVEX lensAstigmatism non-uniform curvature of lens correct with CYLINDER
Refractive Powermeasured in diopters = reciprocal of FOCAL LENGTH (in meters) NORMAL
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Pupillary Dilator opens iris activated by Sympathetic (1)Pupillary Sphincter closes iris activated by Parasympathetic (CN III)
Ciliary Muscle (activated by Parasympathetic CN III)
CONTRACTED LAX suspensory ligaments (zonula fibers) FLAT lensRELAXED TENSE suspensory ligaments (zonula fibers) CURVED lens
Auditory and Vestibular SystemsParts of the EarPart Components Notes
Outer Earpinnaexternal auditory canal
directs sound waves to middle ear
Middle Ear
tympanic membrane
ossicles (malleus, incus, stapes)
Tensor Tympani:CN V, attached to malleus
Stapedius:CN VII, attached to incus
transmits sound waves to inner ear
AIR-filled
SOUND tympanic membranemalleusincus stapes OVAL window
tensor tympani and stapedius causedampening of sound
Inner Ear
BONY MEMBRANOUS organ of hearing (Organ of Corti, located inthe Scala Media on top of Basilar Membrane)FLUID-filled
PERIlympharound ducts(peri)
like ECF Na+, K+
ENDOlymphinside ducts(endo
like ICF Na
+, K
+
Borders of Scala Media1.Reissners Membrane: border with Scala
Vestibuli2.Basilar Membrane: border with Scala
Tympani3.Stria Vascularis: produces endolymph
Components of Organ of Corti1.Outer Hair Cells: PLENTY (3 rows)2.Inner Hair Cells: FEW (1 row only)3.Stereocilia: non-motile cilia on apex of hair
cells4.Tectorial Membrane: gelatinous membrane
on top of hair cells
Scala VestibuliScala TympaniVestibleSemicircularCanals
Scala MediaSemicircular
DuctsUtricleSaccule
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Auditory PathwayNotes
Outer Ear
Tympanic Membrane
Malleus
Incus
Stapes
Amplification of Sound (IMPEDANCE MATCHING)1. mechanical advantage of lever action of malleus and stapes
(malleus has a LONGER lever arm vs. stapes)2. concentration of waves on OVAL window (tympanic membrane is
LARGER than oval window)
OVAL Window
PERILYMPH
sound waves transmitted to perilymph
Cochlea: composed of 2 turnsHelicotrema: apex of cochlea, junction of vestibuli and tympaniOval and Round Windows: base of cochlea
Scala VESTIBULI
helicotrema
Scala TYMPANI
ROUND window
Scala MEDIAOrgan of Corti
Inner Hair Cells:MAJORITY of neuralinformation (~90%)
Outer Hair Cells: MINORcontribution (~10%)
waves in perilymph displace the basilar membrane creates
shearing force BENDING OF HAIR CELLS
BENDING causes changes in K+
conductancebend TOWARDS tallest cilium: DEPOLARIZED(Cochlear
Microphonic Potential (CMP)) release of EXCITATORYNT(Glu or Asp)
bend AWAY FROM tallest cilium: HYPERPOLARIZE
BASE: narrow, stiffHIGH-frequency soundAPEX: wide, loose LOW-frequency sound
Spiral Ganglion 1
s
ORDER NEURONS: nuclei of hair cells
Cochlear Division of CNVIII
Dorsal and VentralCochlear Nuclei
2n
ORDER NEURONS: there could be some crossing-over therefore, central lesions RARELY cause UNILATERAL deafness
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Lateral Lemniscus MAIN ascending auditory tract
Inferior Colliculus
Medial Geniculate Body 3
rORDER NEURONS: analogous to the thalamus
Auditory Radiation
Auditory Cortex
Transverse TemporalGyri of the TemporalLobe
Tonotopic Map: localization of frequencies in the auditory cortex
Main Functions:1. tone discrimination2. sound localization
- differences in time of sound arrival on both sides- differences in sound intensity on both sides
NOTES: Frequency in hertz (Hz)
Intensity in decibles (dB)
rP
Plog20SPL where P is measured sound pressure and Pr is a reference pressure
(0.0002 dyne/cm2
= absolute threshold for human hearing)
Binaural Receptive Fields: neurons above cochlear nuclei respond to stimulation to EITHEREAR 2
oto crossing over of fibers
Lesions to Auditory Pathway
Part DeafnessFrequencyDiscrimination
SoundLocalization
ToneDiscrimination
Ear to CochlearGanglion
UNILATERAL reduced no effect no effect
Lateral Lemniscus toCortex
LITTLE effect no effect reduced reduced
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Vestibular PathwaySemicircular Canals
1. Horizontal2. Superior3. Posterior
ANGULAR acceleration(rotation)
lead to adjustments in the head,eye and postural muscles:1. maintain stable visual image2. maintain balance
Utricle: horizontalSaccule: vertical
LINEAR acceleration(forward/backward/up/down)
ANGULAR ACCELERATION LINEAR ACCELERATION
Organs
Involved
Crista Ampullaris (Ampullary Crest)- located in ampulla at base of
semicircular ducts
Macula Utriculi (in Utricle)Macula Sacculi (in Saccule)
Hair Cells- single Kinocilium- multiple Stereocilia
Cupula- gelatinous membrane ONLY- SAME spec grav as endolymph
Otolith Membrane- gelatinous membrane + CaCO3- GREATER spec grav as endolymph
Generation ofAction Potential
due BENDING of hair cells:
bend TOWARDS kinocilium: DEPOLARIZED release of EXCITATORYNT(Glu or Asp)
bend AWAY FROM kinocilium: HYPERPOLARIZE
ON HEAD TURNING
A. START of turn: endolymph left behindhair cells on side IPSILATERAL to direction of turn: DEPOLARIZEDhair cells on side CONTRALATERAL to direction turn: HYPERPOLARIZED
B. END of turn: endolymph catches uphair cells on side IPSILATERAL to direction of turn: HYPERPOLARIZEDhair cells on side CONTRALATERAL to direction turn: DEPOLARIZED
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Crista Ampullarisin semicircular DUCT
Scarpas Ganglion 1s
ORDER NEURONS: nuclei of hair cells
Vestibular Branch of CN
VIII
Vestibular Nuclei2
nORDER NEURONS: located in the rostral medulla and caudal
pons
Various Projections
Medial Longitudinal Fasciculus (MLF)(Oculomotor Nuclei)
Vestibulo-Ocular Reflex
Lateral Vestibulospinal Tract(POSTURAL muscles)
Vestibulo-Collic ReflexMedial Vestibulospinal Tract(NECKmuscles)
Thalamus then to Cortex conscious sensation
Cerebellum
Reticular Formation
Contralateral Vestibular Complex
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Olfactory PathwayNotes
Olfactory Mucosa(Olfactory Epithelium)
1s
ORDER NEURONS
odorant molecules dissolved in mucus layer activate olfactorychemoreceptors in cilia of the neurons activate Golf that cAMP open cAMP-dependentNa
+channels
DEPOLARIZATION
- receptor cells are TRUE neurons- short half-life (60 days) continuously regenerated from basal
stem cells olfactory neurons are the ONLY neurons capableof regenerating
Olfactory Nerve (CN I)
unmyelinated C fibers small and SLOW
TRIGEMINAL NERVE (CN V): for painful and noxious stimuli
Cribriform Plate
Olfactory Bulb
2n
ORDER NEURONS
Mitral and Tufted Cells: 2nd
Order NeuronsInterneurons (Granule Cells and Periglomerular Cells)
MANY-to-one pattern
Olfactory Tract
Anterior Olfactory Nucleus: contains neurons that project toCONTRALATERAL bulb via the anterior commissure
divides into Lateral and Medial Olfactory StriaeLATERAL prepiriform cortexMEDIAL amygdale and basal forebrain
Prepiriform Cortex
(Olfactory Cortex)
Amygdaloid Nucleusand Basal Forebrain
Quality
combnatn of stimulifrom different chemoreceptors
Intensity overall amount ofneural activity
6 Primary Qualities of Odor
1. floral: rose2. ethereal: pear3. musky: musk4. camphor: eucalyptus5. putrid: rotten eggs6. pungent: vinegar
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Taste PathwayNotes
Taste Chemoreceptorslocated intaste buds
taste chemoreceptors are NOT the 1o
afferent neurons (UNLIKEolfactory chemoreceptors)
Papilla: projections in tongue that contain taste budsAnterior and lateral 2/3: foliate and fungiform papillaePosterior 1/3:circumvallate papillae
Taste Bud: receptors (50-150) + supporting cells + basal cells
- short half-life (10 days) regenerated from basal cells
Chorda Tympani(CN VII)
Glosspharyngeal Nerve(CN IX)
Vagus Nerve(CN X)
anterior 2/3 of tongue posterior 1/3 of tongueback of throat
larynx and epiglottisupper esophagus
1st
ORDER NEURONS
Geniculate Ganglion Petrosal Ganglion Nodose Ganglion
EFFERENT THEN ENTER THE MEDULA
Solitary Tract pathway REMAINS UNCROSSED until the cortex
Solitary Nucleus 2nd
ORDER NEURONS
Ventroposteromedial(VPM) Nucleus of
Thalamus3
rdORDER NEURONS
Gustatory Areas
1. FACEarea ofS12. Insula
Qualitycombnatn of stimulifrom different chemoreceptors
Intensity overall amount ofneural activity
4 Primary Qualities of Taste
1. salty: NaCl
2. sweet: sugar3. sour: HCl4. bitter: quinine
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MOTOR SYSTEMMotor Unit
-motoneuron + muscle fibers = motor unit
SINGLE
Small Large
few msc fibers many msc fibers
threshold firefirst
threshold firelast
small force large force
VARIABLE
Fine Control: FEW fibersLarge Movements:MANYfibers
NOTES: MOTOR UNIT: same neuron, different muscle fibers
MOTONEURON POOL: same muscle group, different neurons
SIZE PRINCIPLE: force of contraction due to the number of motoneurons recruited
Muscle Sensory System
Muscle Spindles Golgi TendonPaccinianCorpuscles
Nociceptors
Info Provided muscle LENGTH muscle TENSIONvibration (highfrequency)
painstimulated by length tension
inhibited by length tension
Location PARALLEL toextrafusals
IN SERIES withextrafusals
embedded insuibcutaneous
free nerve endings
SensoryInnervation
Group Ia fibersGroup II fibers
Group Ib fibers Group II (A-)fibers
Group III: fast painGroup IV: slow pain
MotorInnervation
-motoneurons
Muscle Motor System
EXTRAfusal fibersINTRAfusal fibers
Nuclear Bag Nuclear Chain
Location andMorphology
big fibersbulk of the muscle
PARALLEL to EXTRAfusal fibers
nuclei in a central bag nuclei in a chain
FunctionPRIMARILY MOTOR PRIMARILY SENSORY
generate forcedetect changes inDYNAMIClength detect changes inSTATIClength
SensoryInnervation
Paccinian CorpusclesNociceptors
Group Ia Fibers Group II Fibers
MotorInnervation
-motoneurons -motoneurons to adjust sensitivity of musclespindles
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MUSCLE REFLEX SYSTEMSSTRETCH(MYOTATIC) REFLEX
GOLGI TENDONREFLEX
FLEXORWITHDRAWAL
NUMBER OFSYNAPSES MONOsynaptic DIsynaptic POLYsynaptic
EXAMPLE Knee-Jerk Reflex Clasp-Knife Reflexwithdrawal from a hot
stove
Afferent Arm
Muscle Spindles(Intrafusal fibes)
Golgi Tendon OrganPain Afferents (Free
Nerve Endings)Stimulated: length Stimulated: tension
Inhibited: length Inhibited: tension
Group Ia and II fibers Group Ib fibers Group III and IV fibers
Interneurons NONEINHIBITORY
INTERNEURONMANY
INTERNEURONS
Efferent Arm -motoneuron -motoneuron -motoneuron
EffectAGONIST: contractANTAGONIST: relax
SYNERGIST: activate
AGONIST: relaxANTAGONIST: contract
IPSILATERAL: FlexionFlexors: contractExtensors: relax
CONTRALATERAL:
ExtensionFlexors: relaxExtensors: contract
return muscle tooriginal length
reduce tension inmuscle
IPSILATERAL: moveaway from stimuli
CONTRALATERAL:maintain balance
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Motor Centers and Pathways Pyramidal pass through the medullary PYRAMIDS\
EXTRApyramidal everything else
Originates in Projects to Functions
Pyramidal
CorticospinalTract Primary Motor
Cortex (PrecentralGyrus, Area 6)
Spinal Cord
-motoneuronsvoluntary control of muscles ofthe extremities
CorticobulbarTract
Brain Stem-motoneurons
voluntary control of muscles ofthe head/face
Extrapyramidal
RubrospinalTract
Red NuclesLATERAL spinalcord
control of EXTREMITIES
FLEXORS: Activate
EXTENSORS: InhibitLateralVestibulospinalTract
Deiters NucleusIPSILATERALmoto- andinterneurons
control of TRUNK muscles
FLEXORS: InhibitEXTENSORS: Activate
PontineReticulospinalTract
Pontine ReticularFormation
VENTROMEDIALspinal cord
control of TRUNK muscles
FLEXORS ANDEXTENSORS: Activate
Extensors > Flexors
MedullaryReticulospinalTract
Medullary ReticularFormation
IntermediateGray Area
control of TRUNK muscles
FLEXORS ANDEXTENSORS: Inhibit
Extensors > Flexors
TectospinalTract
Superior ColliculusCERVICALspinal cord
control of NECK muscles
NOTES: CORD TRANSECTIONS
above REDNUCLEUS
Function: activation of extremity FLEXORSloss of inhibition Decorticate Rigidity
above PONTINE
RETICULOSPINAL
Function: activation of trunk FLEXORS AND EXTENSORS
(but extensors > flexors)loss of inhibition Decerebrate Rigidity
above LATERALVESTIBULOSPINAL
Function: activation of trunk EXTENSORSloss of inhibition Decerebrate Rigidity
C1 DEATH
C3 innervations to diaphragm apnea
C7 sympathetic tone to heart bradycardia + hypotension
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SPINAL SHOCK: loss of excitatory input from BOTH - and -motoneurons FLACCIDITY(-motoneuron) and AREFLEXIA (both - and -motoneuron)
MOTOR CORTICES
Premotor + Supplementary Motor Area 6 planning of movementPrimary Motor Area 4 execution of movement
CEREBELLUM3 FUNCTIONAL PARTS OF THE CEREBELLUM
VESTIBULO cerebellum from the vestibular system for balance /eye movement
PONTO cerebellumfrom the motor cortex viapons
. for planning and initiation ofmovement
SPINO cerebellum from the spinefor control of rate, force,range and direction of
movement (synergy)
Flow of Information in the CerebellumINPUT INTEGRATION OUTPUT
Climbing Fibersfrom theINFERIOR OLIVEONLY
Pukinje Cells- multiple synpses,
COMPLEX spikes- conditioning of the Purkinje
fibers, motor learning
PURKINJE CELLS- the ONLY output cells
of the cerebellum- INHIBITORY: uses
GABA
Projections:1. Deep Cerebellar Nuclei2. Vestibular Nuclei
Mossy FibersfromMANYsources
Purkinje Cells- multiple synpses, SIMPLE
spikes
excite
Granular Cells (located inglomeruli)
excite
INHBITORY NEURONS
Basket and Stellate CellsGolgi Type II Cells
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Layers of the Cerebellum innermost outermost
Granular Purkinje Molecular
Cells
3 Gs
1. Golgi Type II2. Granular in (Glomeruli)
Purkinje
Neither G nor PurkinG
1. Basket2. Stellate
Neurites1. dendrites of Purkinje2. axons of granule cells
parallel fibers
BASAL GANGLIA modulates thalamic outflow to cortex to plan and execute SMOOTH movements 4 Parts:
1. Globus Pallidus: receives INPUT from cortex2. Striatum: sends out OUTPUT to cortex and thalamus3. Substantia Nigra4. Subthalamic Nuclei
Pathways of the Basal Ganglia from striatum to cortex
PathwayEffect ofPathway
DopamineReceptor
Effect of Dopamine on Pathway
INDIRECT INHIBITORY D2 inhibitory
inhibitory on inhibitory
(disinhibition) EXCITATORYDIRECT EXCITATORY D1 excitatory excitatory on excitatory
Lesions of the Basal Ganglia1. Globus Pallidus: loss of posture2. Subthalamic Nucleus: disinhibition of CONTRALATERAL side3. Striatum: loss of inhibition (Recall: output of striatum is INHIBITORY)4. Substantia Nigra:Parkinsons Disease (2
oto Dopaminergic neurons lead-pipe rigidity,
tremor, bradykinesia)
HIGHER CORTICAL FUNCTIONSSleep and EEG
Alert, ACTIVE -wavesAlert, RELAXED -wavesSleep SLOW waves
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REM (Rapid Eye Movement)
EEG Pattern S/Sxsoft body, hard dick, fast and small eyes
similar to:
1. AWAKE state2. STAGE 1 Non-REM sleep
- RAPID EYE MOVEMENT ( REM sleep)
- dreams- loss of muscle tone (FLACCIDITY)- pupillary CONSTRICTION- penile ERECTION
Language
RIGHT HemisphereLEFT Hemisphere(L for Language)
NON-VERBAL Language- facial expression- body language- intonation
Spatial Tasks
communicate
viaCORPUSCALLOSUM
VERBAL Language- expressive language
- receptive language(comprehension)
Aphasias damage to the LEFT hemisphere language centers
Speaking Comprehension RESULT
Wernickes
(Receptive)
Wernickes
Area
intact impaired word salad
Brocas(Expressive)
BrocasArea
Impaired intact no output
Temperature Regulation ANTERIOR Hypothalamus compares MEASURED CORE BODY TEMP to SET POINT
TEMP
FEVER- pyrogensINCREASE the set-point hypothalamus perceives core body temp as LESS
than set-point mechanisms INCREASES core body temp- pyrogens IL-1 PG (prostaglandins in hypothalamus set-point)
Heat Stroke: temp causes tissue damageHypothermia: heat generating mechanism cant compensate for tempMalignant Hyperthermia: 2
oto inhaled anesthetics oxidative phosphorylation and heat
production in skeletal muscle
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Notes
Anterior HypothalamusONLY the ANTERIOR hypothalamus can compare set-point withcore body temp
CORE > SET-POINTbody is HOTTER
CORE < SET-POINTbody is HOTTER
ANTERIOR Hypothalamus POSTERIOR Hypothalamus
LOSE HEAT GENERATE HEAT
1. RADIATION and CONVECTION
- cutaneous blood flow (1SYMPATHETIC)
2. EVAPORATION
- sweating (Mus ACh SYMPATHETIC)
1. metabolism thyroid hormones to metabolic rate and heat production
2. lipolysis (BROWN fat)1SYMPATHETIC
3. shiveringMOST POTENTMECHANISM TO
HEAT,
heatproduction by skeletal muscle
RETURN OF CORE TEMP TO SET-POINT
CEREBROSPINAL FLUID (CSF) PHYSIOLOGYNotes:
VENTRICULAR
CHOROID PLEXUS
site of production of CSF located in 2 LATERAL VENTRICLES, 3
rd
VENTRICLE and 4th
VENTRICLE
INDEPENDENT of:a. pressure in ventriclesb. systemic BP
Lateral Vent 1 per hemisphere
Foramen ofMonro
connect lateral vent with3
rdvent
3r
Vent Diencephalon
Aqueduct ofSylvius
Midbrain, connect 3r
vent with 4
thvent
4th
Vent Pons and Medulla
SUBARACHNOID
enters the SUBARACHNOID SPACE throughforamina in the ROOF OF THE 4
thVENT
1 MEDIAL: Magendie (M for Medial)2 LATERAL: Luschka (L for Lateral)
absorption in the SUBARACHNOID VILLIABSORPTION: CSF pressure : absorption(unlike production)
dural venous sinuses systemic circulation
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NOTES: CSF vs. Blood
CSF Na+
and Cl-, equal HCO3
- NaCl to MAINTAIN EQUAL OSMOLARITY
Mg2+
, Crea Glc, CHON, cholesterol, Ca
2+, K
+
High in CREAM, Low SUGAR, CHONCHOLate, CAKe
High in CREA, MgLow in sugar (glucose), CHON, CHOLesterol, Ca
2+, K
+
BLOOD-BRAIN BARRIER (BBB)
Astrocyte Foot Processes + Capillary EndotheliumIMPERMEABLELipid Soluble (non-polar, CO2, O2, H2O): permeable to BBBWater Soluble (polar):NON-permeable to BBB, needs transpoters
Choroid PlexusPERMEABLE area for secretion of substances into the CSF
Functions of the BBB1. maintains environment surrounding neurons CSF is ESSENTIALLY THE SAME as the
ECF of neurons2. prevents escape of neurotransmitters
PHYSIOLOGY OF THE CARDIOVASCULAR SYSTEMHemodynamicsVelocity of Blood Flow
AQVelocity Determinants of Velocity1. Q: amount of blood flow (Cardiac Output)
2. A: total cross-sectional area
blood is SLOWEST at capillaries LARGEST TOTAL areablood is FASTEST at aortaSMALLEST TOTAL area
Quantity of Blood Flow (Cardiac Output)
R
P)CO(Q
Determinants of Cardiac Output
1. P: pressure gradient DRIVER OF FLOW (analogous to voltage)2. R: total peripheral resistance
HINDRANCE TO FLOW (analogousto resistace in electric circuits)
P = MAP RA pressure, where MAP =3
SBPDBP2
Assuming constant Q, if R, there is also in P cause of theGREATEST DROP IN PRESSURE IN THE ARTERIOLES
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Resistance
4r
L8R
Determinants of Resistance
1. : viscosity of blood resistance if with anemia, Hct2. L: length of the vessel
3. r: radius of the vessel
resistance is GREATEST at the arterioles contraction of muscularwall can radius of the vessel
Resistance in Parallel
n21total R
1
R
1
R
1
R
1
TOTAL R < INDIVIDUAL R TOTAL resistance decreases
when there is a branch in anartery
Resistance in Series
Rtotal = R1 + R2 + ... + Rn
TOTAL R > INDIVIDUAL R GREATEST CONTRIBUTOR
to total resistance is theresisatance in the arterioles
Capacitance and ElastanceCapacitance: change in volume per change in pressure measure of DISTENSIBILITYElastance: change in pressure per change in volume measure of RIGIDITY
Capacitance Elastance Determinants of Capacitance and Elastance
PVC
VPE 1. V: change in volume2. P: change in pressure
veins have capacitance they contain a lot ofblood at low pressures (MOST OF THE BLOOD)
Reynolds NumberThe HIGHER THE NUMBER, the HIGHER THE TURBULENCE
Factors affecting Turbulence:1. velocity of flow
2. viscosity
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HEART (LEFT VENTRICLE)
Aorta RESISTANCEVESSELS
THICK walls smooth muscle elastic tissue
HIGH PRESSURE
LOW VOLUME(stressed volume)
Arteries
Arterioles highest RESISTANCE
Capillarieslargest TOTALCROSS-SECTIONALAREA
EXCHANGE OFSUBSTANCES
THINNEST walls(single layer ofepithelium + BM)
Venules
CAPACITANCEVESSELS
THIN walls smooth muscle elastic tissue
LOW PRESSUREHIGH VOLUME(unstressed volume)
Veins
highestCAPACITANCE (containsmost of the blood in thebody)
Vena Cava
HEART (RIGHT ATRIUM)
NOTES:
vessels in SKIN and VISCERA 1-adrenergic receptor CONSTRICTIONvessels in SKELETAL MUSCLES 2-adrenergic receptor DILATATION
Mean PressuresAorta 100 mmHgArterioles 50 mmHg (1/2 of Aorta)Capillaries 20 mmHg (1/5 of Aorta)Vena Cava 4 mmHg (1/25 of Aorta)
Blood Pressures
SBP HIGHEST BP after contraction (systole)DBP LOWEST BP during relaxation (diastole)
Pulse Pressure = SBP - DBP MOST IMPORTANT determinant is STROKE VOLUME
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Electrophysiology of the HeartParts of the ECG
P WaveDEPOLARIZATION of BOTH L and R ATRIA depolarization ONLY, repolarization not seen BURIED in the QRS
complex
PR Intervalfrom the BEGINNING of P to BEGINNING of QRS indicates conduction through the AV node prolonged PR if with
an AV block
QRS Complex DEPOLARIZATION of VENTRICLES
ST Segmentfrom END of S to BEGINNING of T indicates period when the ventricle is still depolarized
QT Intervalfrom BEGINING of QRS to END of T indicates WHOLE period of ventricular depolarization-
repolarization
T Wave REPOLARIZATION of VENTRICLES
Automaticity and Conduction Velocity
AUTOMATICITY CONDUCTION VELOCITY
Definitionability to spontaneously generateaction potentials
time required for excitation to spread
Main Determinant
RATE of slow depolarization inPhase 4 reflects the RATE of the slow
inward Na+
current (If) duringPhase 4
MAGNITUDE of depolarization inPhase 0 reflects SIZE of inward current
(Na+
for conducting ells, Ca2+
forautomatic cells)
Autonomic Effect
CHRONOTROPY: changes in theHEART RATE
positive: HRnegative: HR
DROMOTROPY: changes in theCONDUCTION VELOCITY
positive: velocity, PRnegative: velocity, PR
(NOTE:dromotropy usually refers toconduction through AV Node)
Regulators andMechanism
POSITIVE NEGATIVE POSITIVE NEGATIVE
1Adrenergic: rate of If
MUSACh: rate of If
1Adrenergic: size of inward
Ca2+ current
MUS ACh size of inward
Ca2+ current
Notes: Intrinsic Firing Rates
SA Node (60-100 bpm) > AV Node (40-60 bpm) > His-Purkinje (20-40 bpm)
Conduction VelocitiesFASTEST His-Purkinje System to allow for efficient ventricular contractionSLOWEST AV Node to give ventricle enough time to fill with blood
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The Cardiac Action Potential
Atrial and VentricularMyocardium, Purkinje Fibers
SA Node, AV Node, His-Purkinje System
specialized for CONTRACTION demonstrate AUTOMATICITY
Phase 0
Upstroke
sudden, fastdepolarization
OPENING of voltage-dependent Na
+channels
inward Na+
current
OPENING of Ca2+
channels inward Ca
2+current
IN > OUT depolarization IN > OUT depolarization
Phase 1
INITIALRepolarization
initial ONLYbec of theplateau phase
CLOSURE of voltage-dependent Na
+channels
NO inward Na+
current OPENING of K
+channels
outward K+
current
ABSENT
IN < OUT repolarization
Phase 2
Plateau
equal inwardand outwardcurrents
OPENING of Ca+
channels inward Ca+ channels
STILL OPEN K+
channels outward K
+current
STILL CLOSED Na+
channels NO inward Na+
current
ABSENT
IN = OUT plateau
Phase 3
Repolarization
repolarizationuntil restingpotential
CLOSURE of Ca+
channels inward Ca+ channels
STILL OPEN K+
channels
outward K+ current STILL CLOSED Na
+
channels NO inward Na+
current
CLOSURE of Ca+
channels
NO inward Ca+ channels OPENING of K+
channels outward K
+current
IN < OUT repolarization IN < OUT repolarization
Phase 4
RestingMembranePotential:~ -90 mV
CLOSED Na+ channels LEAKINGK
+channels
brings membrane potential
close to EEq for K+
LEAKINGNa+
channelsinward Na
+current (If)
slowly depolarizes themembrane towards NaEqfor K
+
IN = OUTSTEADY
membrane potential
IN > OUTSLOW
depolarization
once threshold is reached,new action potential is fired BASIS FOR AUTOMATICITY
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NOTES: SUMMARY OF DIFFERENCES
1. Phase 0:Na+
for conducting cells, Ca2+
for automatic cells2. Phase 4:STEADY for conducting cells, SLOWLY DEPOLARIZING for automatic cells
3. ABSENT Phases 1 and 2 for AUTOMATIC cells Ca
2+for CONTRACTION starts from the inward current DURINGPhase 2 (plateau)
entry of Ca2+
causes more Ca2+
to be released from the SARCOPLASMIC RETICULUM(known as Ca
2+-induced Ca
2+release)
Excitability ability to initiate an action potential in response to depolarization reflects RECOVERY of
Na+
channels
(Recall:Na+ channels are INACTIVATED during depolarization; they RECOVER duringrepolarization/hyperpolarization)
Absolute Refractory Effective Refractory Relative Refractory Supranormal
from start of Phase 0to end of Phase 2
similar to ARP, justslightly longer
from end of Phase 2to start of Phase 4(i.e. from end ofARP to completionof repolarization)
shortly after the endof RelativeRefractory Period
NO action potential can be generated AT ALL
action potential CANbe generated ONLYIF with strongstimulus
action potential CANbe generated EVENWITH weakstimulus
The MyocardiumStructure: SIMILAR to skeletal muscle
SARCOMERE is also the contractile unit of myocardiumSTRIATED appearance also follows the Sliding Filament Model for contraction/shortening actin is pulled towards
the center of the sarcomere
DIFFERENCES WITH SKELETAL MUSCLE1. branching pattern (rather than parallel)2. more mitochondria
3. T-tubules form dyads with SR (rather than triads)4. presence of INTERCALATED DISCS (absent in skeletal muscle) connections between sarcomeres at their ends contain GAP JUNCTIONS provide direct communication between cells for
FASTER spread of action potentials(electrical syncytium)
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Excitation-Contraction Coupling in Myocardium
Myocardium receives actionpotential from:
1. SA Node2. AV Node3. Purkinje fibers4. other myocardial cells
Action potential travels tointerior of cell through T-tubules
t-tubules follow the Z-lines going to the interior of the cell
T-tubules stimulate SR torelease stored Ca
2+
Determinants of amount of Ca2+
release:1. amount of Ca2+ stored in SR SR gets Ca
2+via a Ca
2+/ATPase pump then
sequesters it via Calsequestrin
2. amount of inward Ca2+
current Ca
2+-Induced Ca
2+release Ca
2+derived from inward
current during the Plateau/Phase 2
Ca2+
binds to Troponin C Tropomyosin moves away from actin binding site
Myosin binds to actin bindingsite in the ABSENCE of ATP
if WITH ATP: binding RELEASED can relaxif WITHOUT ATP: binding PRESENT cant relax
in death, muscles become rigid due to the absence ofATP (rigor mortis)
ATP binds to myosin to release
myosin from actin
ATP hydrolyzed to ADP + Pi to
move the myosin head to theplus end of actin
ADP released myosin binds to a NEW binding site in actin
(Recall:myosin is bound to actin if there isNO ATP)
ATP binds to myosin AGAIN torepeat the cycle
the cycle will repeat as long as:1. there is ATP: to cause dissociation and movement2. there is Ca
2+: to move tropomyosin out of the way
Ca2+
taken back by SR RELAXATION occurs when there is no longer any Ca
2+
tropomyosin once again blocks actins binding site
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Contractility (Inotropism) ability of cardiac muscle to develop tension at any given length TENSION DEVELOPED DEPENDS ON THE AMOUNT OF INTRACELLULAR Ca
2+
HR Rate CHRONOtropy from RATE of inward Na
+
currentConduction Velocity DROMOtropy from SIZE of inward Ca2+
currentContractility INOtropy from AMOUNT of intracellular Ca
2+
POSITIVE Inotropy NEGATIVE Inotropy
Definition STRONGER contraction WEAKER contraction
Mechanism GREATER intracellular Ca+
GREATER inward Ca2+
currentLESS intracellular Ca
+
LESS inward Ca2+
current
Factorscausing...
1. HRa. Positive Staircase
(Bowditch Staircase):
HR Ca2+
accumulatewith each heartbeat
b. ExtrasystolicPotentiation: excess Ca
2+
immediately after theextrasystole
2. 1 adrenergic stimulation:a. inward Ca
2+current
during plateaub. Ca
2+sequestration by
SR (phosphorylation ofPhospholamban)
3. Cardiac Glycosides: inhibitNa
+/K
+/ATPase Na
+
Na+/Ca
2+cotransport Ca
2+
accumulates in cell
1. MuscarinicAcetylcholinergic: inwardCa
2+current during plateau
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Length-Tension Relationships (Frank-Starling)
LENGTH-TENSION FORCE-VELOCITY
Kind ofContraction
ISOMETRIC ISOTONIC
Tension varying ConstantLength constant varying (velocity)
GraphX-AxisY-Axis
length: PRELOADtension
tension: AFTERLOADchange in length (velocity)
Relationship PARABOLIC
length tensionUNTIL acertain MAX stretching maximizes the
number of possible cross-links
between actin and myosin
further length tension further stretching brings binding
sites in actin FARTHER frommyosin LESS binding sites
TENSION IS MAX AT AN IDEALPRELOAD
NEGATIVE SLOPE
tension/afterload velocity msc must contract AGAINST a
stronger force
VELOCITY IS MAX IFAFTERLOAD ZERO
NOTES:
PRELOAD length of muscle BEFORE contraction LV end-diastolic volumeAFTERLOAD tension AGAINST WHICH msc contracts aortic/pulm artery pressure
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Ventricular Pressure Volume Loops
startswith...
in between... endswith...
SignificanceVol PressISOVOLUMETRICContraction
closure ofmitral valve
CONSTANT INCopening ofaortic valve
ventricle contracts to
pres but LV pres aortic presblood leaves the ventricleleading to in vol
if aortic pres > LV pres,aortic valve closes nofurther in volume
Volume at END: END-SYSTOLIC VOLUME
ISOVOLUMETRICRelaxation
closure ofaortic valve
CONSTANT DECopening ofmitral valve
ventricle relaxes causing in LV pres butLV pres > LA presmitral valve remainsclosed
VentricularRelaxation
opening ofmitral valve
INCSLOW
INCclosure ofmitral valve
LV pres < LA presMVopens and blood rushesto LV leading to in vol
ventricle contractscausing in pres: onceLV pres > LA pres, mitralvalve closes no further in volume
Volume at END: END-DIASTOLIC VOLUME
NOTES: WIDTH OF LOOP reflects stroke volume
HEIGHT OF LOOP reflects afterload (aortic pres)
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Volume
Pressure
stroke volume
end-diastolicvolume
end-systolicvolume
Effects to Loop
Increasing Preloadincreased end-diastolic volume
Increasing Afterloadincreased aortic pressure
Increasing Contractilitypositive inotropes
increased end-diastolicvolume: loop widenstowards the right
increased contractility(Frank-Starling) strokevolume: left boundary ofloop does NOT change
aortic valve opens at ahigher pressure: loopbecomes taller
stroke volume: loopbecomes narrower
end-systolic volume:left boundary displaced toright
stroke volume: loopwidens
end-systolic volume: leftboundary displaced to left
Volume
Pressure
newloop
Volume
Pressure
newloop
Volume
Pressure
new
loop
OVERALL: loop WIDENS tothe RIGHT
OVERALL: loop NARROWSto the RIGHT, and becomesTALLER
OVERALL: loop WIDENS to theLEFT
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Cardiac Output (Cardiac Function) and Venous Return (Vascular Function) Curve End-Diastolic Volume CO (2o to Frank-Starling Law) Right Atrial Pressure venous return
Mean SYSTEMIC Pressure right atrial pressure at which there is NO flow of blood- ABSENT P between blood pressure and RA nothing drives blood to flow to RA- intersection between venous return curve and the x-axis
RA Pressure orEnd-Diastolic Volume
VenousReturnor
CardiacOutput Cardiac Output
Venous Return
Mean SystemicPressure
Changing the SHAPE of the Graph
Venous ReturnBlood Volume and Venous Capacitance- SAME slope, DIFFERENT Mean Systemic Pressure
BLOOD VOLUME or CAPACITANCE
RA Pressure
VenousReturn
NEWMeanSystemic
Pressure
1. venous return for ALL RA pressure
shift to R2. mean systemic pressureshift to R
BLOOD VOLUME or CAPACITANCE
RA Pressure
VenousReturn
NEW MeanSystemic
Pressure
1. venous return for ALL RA pressure
shift to L2. mean systemic pressureshift to L
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Total Peripheral Resistance- DIFFERENT slope, SAME Mean Systemic Pressure
RESISTANCE
RA Pressure
VenousReturn
venous return for ALL RA pressure butSAME mean systemic pressure slope
RESISTANCE
RA Pressure
VenousReturn
venous return for ALL RA pressure butSAME mean systemic pressure slope
Cardiac Output
Inotropes- SAME x-axis, DIFFERENT slopes
POSITIVE Inotropes
End-Diastolic Volume
CardiacOu
tput
NEWCO
CO for ALL EDV slope
NEGATIVE Inotropes
End-Diastolic Volume
CardiacOu
tput
NEWCO
CO for ALL EDV slopeEQUILIBRIUM or STEADY-STATE POINT: point at which CO and venous return are equal
- can be altered by changing the shape of CO and venous return curves:1. use inotropes2. change total peripheral resistance3. change venous return or venous capacitance
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Stroke Volume Cardiac Output Ejection Fraction
volume ejected by heart perheartbeat (50-80 mL)
volume ejected by heart perminute (~ 5 L)
fraction of end-DIASTOLICvolume ejected per heartbeat(55%)
SV = End-Diastolic VolEnd-Systolic Vol
CO = SV x HREDV
SVEF
Cardiac Output by the FICK PRINCIPLE
)arterypulmonaryO()veinpulmonaryO(
nConsumptioOTOTALCO
22
2
1. determine TOTAL O2 consumption2. O2 Pulmonary Vein = O2 content of PERIPHERAL ARTERY both OXYGENATED
3. O2 Pulmonary Artery = O2 content of MIXED VENOUS BLOOD
both DEOXYGENATED
Stroke Work- work performed by heart per heartbeat
W = Force x Distance = P x VW = (Aortic Pressure) x (Stroke Volume)
- reflect O2 consumption of the heart- Fatty Acids: primary energy source for myocardium
Factors that INCREASE work:1. increased afterload heart must contract AGAINST a load2. increased HR heart does more in a minute3. increased contractility stroke volume increases4. increased size radius = tension
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The Cardiac Cycle: 7 StepsEvent Description ECG Notes
1 Atrial Systole
START:atrial systole
END: mitralvalve closure
atria contracts (atrialkick)
blood ejected toventricle
P wave NOT ESSENTIAL for ventricular filling(30% of ventricular filling only)
Heart Sounds: 4th
sound (due to rushof blood to LV)
LV Pressure: slight LV Volume: at its peak
(due to ending of LV filling) Aortic Pressure: dropping Venous Pulse: a wave (due to atrial
contraction)
2 IsovolumetricVentricularContraction
START:mitral valveclosure
END: aorticvalve opening
ventricle contracts, butwith NO CHANGE involume
mitral valve closes (LV> LA)
aortic valve still closed(LV < aorta)
QRScomplex
Heart Sounds: 1s sound (due tomitral valve closure)
LV Pressure: rapid (due toventricular contraction)
LV Volume: constant (ISOvolumetricsince all valves still closed)
Aortic Pressure: stilldropping
(no flow into aorta yet) Venous Pulse: c wave (due to closure
ofTRICUSPIDvalve)3 Rapid
VentricularEjection
START:aortic valveopening
END: peak ofventricular
pressure
RAPID ejection ofblood into aorta
PEAK ventricularpressure reached
aortic valve opens (LV> aorta) blood flowsout of LV and into theaorta
ONSETof Twave
Heart Sounds: NONE
LV Pressure: continued until MAX(ventricle still contracting)
LV Volume: rapid (blood beingemptied to the aorta)
Aortic Pressure: rapid until MAX(aortic valve opens and blood flows toaorta)
Venous Pulse: c wave (due to closureofTRICUSPIDvalve)
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Event Description ECG Notes
4 ReducedVentricularEjection
START:peak ofventricularpressure
END: aorticvalve closure
SLOWER ejection ofblood into aorta
aortic valve closes (LV< aorta) flow ofblood stops
atria starts to fill
T wave Heart Sounds: 2n
sound (due toaortic valve closure)
LV Pressure: start of LV Volume: continued until MIN
(ventricle already being emptied ofblood)
Aortic Pressure: start of untilincisura (or dicrotic notch)(due to runoff of blood to periphery,while incisura due to closure of aorticvalve)
Venous Pulse: starts to (due toatrial filling)
5 IsovolumetricVentricularRelaxation
START:aortic valveclosure
END: mitralvalve opening
ventricle relaxes, butwith NO CHANGE involume
mitral valve still closed(LV > LA)
aortic valve closes(LV < aorta)
atria continue to fill
END ofT wave
Heart Sounds: NONE
LV Pressure: until MIN(due toventricular relaxation)
LV Volume: constant(ISOvolumetricsince all valves still closed)
Aortic Pressure: initially then (initialdue to closure of aortic valve,while nextdue to runoff of blood)
Venous Pulse: v wave (due to peak ofatrial filling)
6 RapidVentricularFilling
START:mitral valveopening
END: peak ofventricularvolume
PEAK of atrialpressure
mitral valve opens (LV< LA)RAPID flowof blood into LV
BET Tand Pwaves
Heart Sounds: 3r
sound (due to rushof blood to LV)
LV Pressure: still (due tocompliance of ventricle)
LV Volume: rapid (due to rapidentry of blood to LV)
Aortic Pressure: still (due to runoffto periphery, aortic valve still closed)
Venous Pulse:(due to emptying ofaorta)
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Event Description ECG Notes
7 ReducedVentricularFilling
(Diastasis)
START:peak ofventricularvolume
END: atrialsystole
SLOWER flow ofblood to LV
BET Tand Pwaves
LONGEST PART of the cardiac cycle most affected by changes in HR
Heart Sounds: NONE
LV Pressure: still (due tocompliance of ventricle)
LV Volume: slower (due to slowedentry of blood to LV)
Aortic Pressure: still (due to runoffto periphery, aortic valve still closed)
Venous Pulse: starting to (due toreduction in rate of emptying of aorta)
NOTES: HEART SOUNDS
1st
Heart Sound MV/TV closure start of Isovolumetric Ventricular Contraction2
ndHeart Sound AV/PV closure end of Reduced Ventricular Ejection
3rd
Heart Sound rush of bloodt to LV start of Rapid Ventricular Filling4
thHeart Sound atrial kick Atrial Systole
ECG PARTSP Wave Atrial Depolarization Atrial SystoleQRS Complex Ventricular Depolarization Isovolumetric Ventricular Contraction
ONSET of T ONSET of Repolarization start of Reduced Ventricular FillingT Wave Ventricular Repolarization Isovolumetric Ventricular Relaxation
VENOUS PRESSURE WAVESa Wave AtrialSystole Atrial Systolec Wave closure of tricuspid start of Isovolumetric Ventricular Contractionv Wave peak of atrial filling end of Isovolumetric Ventricular Relaxation
VENTRICULAR PRESSURE AND VOLUMEVolume PEAK end of Atrial SystoleVolume MIN end of Reduced Ventricular Ejection
Pressure PEAK end of Rapid Ventricular EjectionPressure MIN end of Isovolumetric Ventricular Relaxation
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`JPGEsteban PediaNotesPhysiology NotesChino Espino, MD
58All rights reserved. 2010.
Regulation of Blood PressureBaroreceptor Reflex Renin-Angiotensin-Aldosterone
Mode ofAction
NEURAL HORMONAL
Onset andDuration
rapid onsetfast duration (minute-to-minutechanges)
slow onsetlong-term duration
Receptors Baroreceptors (Carotid SINUS)- in wall of bifurcation of common
carotid and in aortic arch
Juxtaglomerular Apparatus- in kidney
StimulusDetected
stretch of wall
carotid sinus: REDUCTION in stretchaortic arch: