Neuromuscular A&P Special lecture powerpoint assembled by T.A. Trendler for her wonderful PHYSO 2A class in Fall 2008 From Saladin’s A&P Chapters 5, 11.

Neuromuscular A&PNeuromuscular A&PSpecial lecture powerpoint assembled by T.A. TrendlerSpecial lecture powerpoint assembled by T.A. Trendler

for her wonderful PHYSO 2A class in Fall 2008for her wonderful PHYSO 2A class in Fall 2008

From Saladin’s A&P Chapters 5, 11 & 12*From Saladin’s A&P Chapters 5, 11 & 12*

Given November 10 & 12Given November 10 & 12

OverviewOverview

• Given only 2 days to cover 2 really important Given only 2 days to cover 2 really important chapterschapters

• I decided to integrate the main topics I decided to integrate the main topics powerpointpowerpoint

• We’ll cover the anatomy on MondayWe’ll cover the anatomy on Monday

• Then the physiology on WednesdayThen the physiology on Wednesday• Okay? Okay?

MyOLOGyMyOLOGy

Myology: study of muscular tissues (Chapter 5 in Myology: study of muscular tissues (Chapter 5 in Saladin)Saladin)

Myo: latin for muscle (mus = mouse, -cle = little)Myo: latin for muscle (mus = mouse, -cle = little)

Sarco: greek for flesh/body (think sarcophagus, body Sarco: greek for flesh/body (think sarcophagus, body box)box)

Muscle tissue characteristics:Muscle tissue characteristics:

excitable, conductive, contractile & extensible*excitable, conductive, contractile & extensible*

*elasticity due to connective tissues*elasticity due to connective tissues

Functions:Functions:

Motion of body parts (or substances in body)Motion of body parts (or substances in body)

Stability of body parts (or substances in body)Stability of body parts (or substances in body)

Heat production (basal metabolic rate & shivering)Heat production (basal metabolic rate & shivering)

Types of Muscle TissueTypes of Muscle Tissue

Skeletal* muscle tissueSkeletal* muscle tissue

striated & voluntarystriated & voluntary

studied as the muscular systemstudied as the muscular system

Cardiac muscle tissueCardiac muscle tissue

striated & autorhythmicstriated & autorhythmic

Smooth muscle tissueSmooth muscle tissue

nonstriated & involuntarynonstriated & involuntary

Skeletal MuscleSkeletal Muscle

• Long, cylindrical, unbranched cells with Long, cylindrical, unbranched cells with striations and multiple peripheral nucleistriations and multiple peripheral nuclei• movement, facial expression, posture, movement, facial expression, posture,

breathing, speech, swallowing and excretionbreathing, speech, swallowing and excretion

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Muscular DystrophyMuscular Dystrophy• Hereditary diseases - skeletal muscles degenerate Hereditary diseases - skeletal muscles degenerate

and are replaced with adiposeand are replaced with adipose

• Disease of malesDisease of males• appears as child begins to walkappears as child begins to walk• rarely live past 20 years of agerarely live past 20 years of age

• Dystrophin links actin filaments to cell membraneDystrophin links actin filaments to cell membrane• leads to torn cell membranes and necrosisleads to torn cell membranes and necrosis

• Fascioscapulohumeral MD -- facial and shoulder Fascioscapulohumeral MD -- facial and shoulder muscle onlymuscle only

11-11-77

Myasthenia GravisMyasthenia Gravis• Autoimmune disease - antibodies attack NMJ and Autoimmune disease - antibodies attack NMJ and

bind ACh receptors in clustersbind ACh receptors in clusters• receptors removedreceptors removed• less and less sensitive to AChless and less sensitive to ACh

• drooping eyelids and double vision, difficulty swallowing, drooping eyelids and double vision, difficulty swallowing, weakness of the limbs, respiratory failureweakness of the limbs, respiratory failure

• Disease of women between 20 and 40Disease of women between 20 and 40

• Treated with cholinesterase inhibitors, thymus Treated with cholinesterase inhibitors, thymus removal or immunosuppressive agentsremoval or immunosuppressive agents

11-11-88

Myasthenia GravisMyasthenia Gravis

Drooping eyelids and weakness of muscles of eye movement

Cardiac MuscleCardiac Muscle

• Short branched cells with striations and Short branched cells with striations and intercalated discsintercalated discs• one central nuclei per cellone central nuclei per cell

• Pumping of blood by cardiac (heart) Pumping of blood by cardiac (heart) musclemuscle

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Cardiac Muscle 1Cardiac Muscle 1

• Thick cells shaped like a log with uneven, notched Thick cells shaped like a log with uneven, notched endsends

• Linked to each other at intercalated discsLinked to each other at intercalated discs• electrical gap junctions allow cells to stimulate their electrical gap junctions allow cells to stimulate their

neighborsneighbors• mechanical junctions keep the cells from pulling apartmechanical junctions keep the cells from pulling apart

• Sarcoplasmic reticulum less developed but large T Sarcoplasmic reticulum less developed but large T tubules admit Ca+2 from extracellular fluidtubules admit Ca+2 from extracellular fluid

• Damaged cells repaired by fibrosis, not mitosisDamaged cells repaired by fibrosis, not mitosis

11-11-1111

Cardiac Muscle 2Cardiac Muscle 2

• Autorhythmic due to pacemaker cellsAutorhythmic due to pacemaker cells

• Uses aerobic respiration almost exclusivelyUses aerobic respiration almost exclusively• large mitochondria make it resistant to fatiguelarge mitochondria make it resistant to fatigue• very vulnerable to interruptions in oxygen very vulnerable to interruptions in oxygen

supplysupply

Smooth MuscleSmooth Muscle

• Short fusiform cells; nonstriated with only one Short fusiform cells; nonstriated with only one central nucleuscentral nucleus• sheets of muscle in viscera; iris; hair sheets of muscle in viscera; iris; hair

follicles and sphincters follicles and sphincters • swallowing, GI tract functions, labor swallowing, GI tract functions, labor

contractions, control of airflow, erection of contractions, control of airflow, erection of hairs and control of pupilhairs and control of pupil

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Smooth MuscleSmooth Muscle• Fusiform cells with one nucleusFusiform cells with one nucleus

• 30 to 200 microns long and 5 to 10 microns wide30 to 200 microns long and 5 to 10 microns wide• no striations, sarcomeres or Z discsno striations, sarcomeres or Z discs• thin filaments attach to dense bodies scattered thin filaments attach to dense bodies scattered

throughout sarcoplasm and on sarcolemmathroughout sarcoplasm and on sarcolemma• SR is scanty and has no T tubulesSR is scanty and has no T tubules

• calcium for contraction comes from extracellular fluidcalcium for contraction comes from extracellular fluid

• If present, nerve supply is autonomicIf present, nerve supply is autonomic• releases either ACh or norepinephrinereleases either ACh or norepinephrine

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Types of Smooth MuscleTypes of Smooth Muscle

• Multiunit smooth muscleMultiunit smooth muscle• largest arteries, iris, pulmonary air passages, largest arteries, iris, pulmonary air passages,

arrector pili musclesarrector pili muscles• terminal nerve branches synapse on myocytesterminal nerve branches synapse on myocytes• independent contractionindependent contraction

11-11-1515

Types of Smooth MuscleTypes of Smooth Muscle

• Single-unit smooth muscleSingle-unit smooth muscle• most blood vessels and viscera as circular and most blood vessels and viscera as circular and

longitudinal muscle layerslongitudinal muscle layers• electrically coupled by gap junctionselectrically coupled by gap junctions• large number of cells contract as a unitlarge number of cells contract as a unit

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Stimulation of Smooth Stimulation of Smooth MuscleMuscle

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Stimulation of Smooth Stimulation of Smooth MuscleMuscle

• Involuntary and contracts without nerve stimulationInvoluntary and contracts without nerve stimulation• hormones, CO2, low pH, stretch, O2 deficiencyhormones, CO2, low pH, stretch, O2 deficiency• pacemaker cells in GI tract are autorhythmicpacemaker cells in GI tract are autorhythmic

• Autonomic nerve fibers have beadlike swellings called Autonomic nerve fibers have beadlike swellings called varicosities containing synaptic vesiclesvaricosities containing synaptic vesicles• stimulates multiple myocytes at diffuse junctionsstimulates multiple myocytes at diffuse junctions

11-11-1818

Features of Contraction and RelaxationFeatures of Contraction and Relaxation

• Calcium triggering contraction is Calcium triggering contraction is extracellularextracellular• calcium channels triggered to open by voltage, calcium channels triggered to open by voltage,

hormones, neurotransmitters or cell stretchinghormones, neurotransmitters or cell stretching• calcium ions bind to calmodulincalcium ions bind to calmodulin• activates light-chain myokinase which activates myosin activates light-chain myokinase which activates myosin

ATPase ATPase • power stroke occurs when ATP hydrolyzedpower stroke occurs when ATP hydrolyzed

• Thin filaments pull on intermediate filaments Thin filaments pull on intermediate filaments attached to dense bodies on the plasma attached to dense bodies on the plasma membranemembrane• shortens the entire cell in a twisting fashionshortens the entire cell in a twisting fashion

11-11-1919

• Contraction and relaxation very slow in Contraction and relaxation very slow in comparisoncomparison• slow myosin ATPase enzyme and slow pumps slow myosin ATPase enzyme and slow pumps

that remove Ca+2that remove Ca+2

• Uses 10-300 times less ATP to maintain the Uses 10-300 times less ATP to maintain the same tensionsame tension• latch-bridge mechanism maintains tetanus latch-bridge mechanism maintains tetanus

(muscle tone)(muscle tone)• keeps arteries in state of partial contraction keeps arteries in state of partial contraction

(vasomotor tone)(vasomotor tone)

Features of Contraction and Features of Contraction and RelaxationRelaxation

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Contraction of Smooth Contraction of Smooth MuscleMuscle

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Responses to StretchResponses to Stretch

• Stretch opens mechanically-gated calcium channels causing Stretch opens mechanically-gated calcium channels causing muscle responsemuscle response• food entering the esophagus brings on peristalsisfood entering the esophagus brings on peristalsis

• Stress-relaxation response necessary for hollow organs that Stress-relaxation response necessary for hollow organs that gradually fill (urinary bladder)gradually fill (urinary bladder)• when stretched, tissue briefly contracts then relaxeswhen stretched, tissue briefly contracts then relaxes

• Must contract forcefully when greatly stretchedMust contract forcefully when greatly stretched• thick filaments have heads along their entire lengththick filaments have heads along their entire length• no orderly filament arrangement -- no Z discsno orderly filament arrangement -- no Z discs

• Plasticity is ability to adjust tension to degree of stretch Plasticity is ability to adjust tension to degree of stretch such as empty bladder is not flabbysuch as empty bladder is not flabby

““Gross” Muscle AnatomyGross” Muscle Anatomy

Skeletal muscles are organsSkeletal muscles are organs

Muscle cells Muscle cells are called “are called “fibersfibers” (myofibers)” (myofibers)

Nervous tissue -> sensory & motor neuronsNervous tissue -> sensory & motor neurons

Blood vessels (lined by epithelia)Blood vessels (lined by epithelia)

Connective tissue wrappersConnective tissue wrappers

endomysium, perimysium, epimysium, fascia, endomysium, perimysium, epimysium, fascia,

tendons vs. aponeurosestendons vs. aponeuroses

collagen is extensible and elastic*collagen is extensible and elastic*

A MyofiberA Myofiber

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MYOFiber specializationsMYOFiber specializations

Multiple flattened nuclei just inside cell membraneMultiple flattened nuclei just inside cell membrane• fusion of multiple myoblasts during developmentfusion of multiple myoblasts during developmentsatellite cells nearby can multipy/produce some new satellite cells nearby can multipy/produce some new

myofibers myofibers Sarcolemma with transverse (T) tubules that penetrate the Sarcolemma with transverse (T) tubules that penetrate the

cellcell• carry electric current to cell interiorcarry electric current to cell interior

Sarcoplasm is filled with Sarcoplasm is filled with • myofibrils (bundles of myofilaments)myofibrils (bundles of myofilaments)• glycogen for stored energy and myoglobin for binding glycogen for stored energy and myoglobin for binding

oxygenoxygen

Sarcoplasmic reticulum = smooth ERSarcoplasmic reticulum = smooth ER• network around each myofibrilnetwork around each myofibril• dilated end-sacs (terminal cisternae) store calciumdilated end-sacs (terminal cisternae) store calcium• triad = T tubule and 2 terminal cisterneatriad = T tubule and 2 terminal cisternea

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Thick FilamentsThick Filaments

• Made of 200 to 500 myosin moleculesMade of 200 to 500 myosin molecules• 2 entwined polypeptides (golf clubs)2 entwined polypeptides (golf clubs)

• Arranged in a bundle with heads directed outward in Arranged in a bundle with heads directed outward in a spiral array around the bundled tailsa spiral array around the bundled tails• central area is a bare zone with no headscentral area is a bare zone with no heads

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Thin FilamentsThin Filaments• Two intertwined strands fibrous (F) actin Two intertwined strands fibrous (F) actin

• globular (G) actin with an active siteglobular (G) actin with an active site

• Groove holds tropomyosin moleculesGroove holds tropomyosin molecules• each blocking 6 or 7 active sites of G actinseach blocking 6 or 7 active sites of G actins

• One small, calcium-binding troponin molecule on One small, calcium-binding troponin molecule on each tropomyosin moleculeeach tropomyosin molecule

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Elastic FilamentsElastic Filaments

• Springy proteins called titinSpringy proteins called titin

• Anchor each thick filament to Z discAnchor each thick filament to Z disc

• Prevents overstretching of sarcomerePrevents overstretching of sarcomere

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Regulatory vs. Contractile ProteinsRegulatory vs. Contractile Proteins

• Myosin and actin are contractile proteinsMyosin and actin are contractile proteins

• Tropomyosin and troponin = regulatory proteinsTropomyosin and troponin = regulatory proteins• switch that starts and stops shortening of muscle cellswitch that starts and stops shortening of muscle cell• contraction activated by release of calcium into contraction activated by release of calcium into

sarcoplasm and its binding to troponin, sarcoplasm and its binding to troponin, • troponin moves tropomyosin off the actin active sitestroponin moves tropomyosin off the actin active sites

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Overlap of Thick and Thin Overlap of Thick and Thin FilamentsFilaments

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Striations = Organization of FilamentsStriations = Organization of Filaments

• Dark A bands (regions) alternating with lighter I bands (regions)Dark A bands (regions) alternating with lighter I bands (regions)• anisotrophic (A) and isotropic (I) stand for the way these regions affect anisotrophic (A) and isotropic (I) stand for the way these regions affect

polarized lightpolarized light

• A band is thick filament regionA band is thick filament region• lighter, central H band area contains no thin filamentslighter, central H band area contains no thin filaments

• I band is thin filament regionI band is thin filament region• bisected by Z disc protein called connectin, anchoring elastic and thin filamentsbisected by Z disc protein called connectin, anchoring elastic and thin filaments• from one Z disc (Z line) to the next is a sarcomerefrom one Z disc (Z line) to the next is a sarcomere

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Striations and Striations and SarcomeresSarcomeres

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Relaxed and Contracted Relaxed and Contracted SarcomeresSarcomeres

• Muscle cells shorten because their individual Muscle cells shorten because their individual sarcomeres shorten sarcomeres shorten • pulling Z discs closer togetherpulling Z discs closer together• pulls on sarcolemmapulls on sarcolemma

• Notice neither thick nor thin filaments Notice neither thick nor thin filaments change length during shorteningchange length during shortening

• Their overlap changes as sarcomeres Their overlap changes as sarcomeres shortenshorten

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Nerve-Muscle Nerve-Muscle RelationshipsRelationships

• Skeletal muscle must be stimulated by a nerve or Skeletal muscle must be stimulated by a nerve or it will not contractit will not contract

• Cell bodies of somatic motor neurons in brainstem Cell bodies of somatic motor neurons in brainstem or spinal cord or spinal cord

• Axons of somatic motor neurons = somatic motor Axons of somatic motor neurons = somatic motor fibersfibers• terminal branches supply one muscle fiberterminal branches supply one muscle fiber

• Each motor neuron and all the muscle fibers it Each motor neuron and all the muscle fibers it innervates = motor unitinnervates = motor unit

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Motor UnitsMotor Units• A motor neuron and the muscle A motor neuron and the muscle

fibers it innervatesfibers it innervates• dispersed throughout the muscledispersed throughout the muscle• when contract together causes weak when contract together causes weak

contraction over wide areacontraction over wide area• provides ability to sustain long-term provides ability to sustain long-term

contraction as motor units take turns contraction as motor units take turns resting (postural control)resting (postural control)

• Fine controlFine control• small motor units contain as few as small motor units contain as few as

20 muscle fibers per nerve fiber20 muscle fibers per nerve fiber• eye muscleseye muscles

• Strength controlStrength control• gastrocnemius muscle has 1000 gastrocnemius muscle has 1000

fibers per nerve fiberfibers per nerve fiber

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Neuromuscular Junctions Neuromuscular Junctions (Synapse)(Synapse)

• Functional connection between Functional connection between nerve fiber and muscle cellnerve fiber and muscle cell

• Neurotransmitter (acetylcholine/ACh) released Neurotransmitter (acetylcholine/ACh) released from from nerve fiber stimulates muscle cell nerve fiber stimulates muscle cell

• Components of synapse (NMJ)Components of synapse (NMJ)• synaptic knob is swollen end of nerve fiber synaptic knob is swollen end of nerve fiber

(contains ACh)(contains ACh)• junctional folds region of sarcolemmajunctional folds region of sarcolemma

• increases surface area for ACh receptorsincreases surface area for ACh receptors• contains acetylcholinesterase that breaks down ACh and contains acetylcholinesterase that breaks down ACh and

causes relaxationcauses relaxation• synaptic cleft = tiny gap between nerve and muscle synaptic cleft = tiny gap between nerve and muscle

cellscells• Basal lamina = thin layer of collagen and Basal lamina = thin layer of collagen and

glycoprotein over all of muscle fiberglycoprotein over all of muscle fiber

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The Neuromuscular The Neuromuscular JunctionJunction

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Neuromuscular ToxinsNeuromuscular Toxins• Pesticides (cholinesterase inhibitors) Pesticides (cholinesterase inhibitors)

• bind to acetylcholinesterase and prevent it from bind to acetylcholinesterase and prevent it from degrading AChdegrading ACh

• spastic paralysis and possible suffocationspastic paralysis and possible suffocation

• Tetanus or lockjaw is spastic paralysis caused by Tetanus or lockjaw is spastic paralysis caused by toxin of toxin of ClostridiumClostridium bacteria bacteria• blocks glycine release in the spinal cord and causes blocks glycine release in the spinal cord and causes

overstimulation of the musclesoverstimulation of the muscles

• Flaccid paralysis (limp muscles) due to curare that Flaccid paralysis (limp muscles) due to curare that competes with AChcompetes with ACh• respiratory arrestrespiratory arrest

End of Lecture 11aEnd of Lecture 11a

• During labDuring lab• see slides of all three muscle tissuessee slides of all three muscle tissues• look at models of samelook at models of same• review muscles (organs)review muscles (organs)