BASIM ZWAIN LECTURE NOTESBASIM ZWAIN LECTURE NOTES

MuscleMuscle

ExitExit HomeHome

SkeletalSkeletal (striated, voluntary), (striated, voluntary), cardiaccardiac (striated, inv- (striated, inv-oluntary), oluntary), smoothsmooth (non-striated, involuntary). (non-striated, involuntary). Common featuresCommon features: elongated cells (fibers), myofila-: elongated cells (fibers), myofila-ments (actin&myosin), comprised of: fibers, CT, ments (actin&myosin), comprised of: fibers, CT, blood vessels & nervous tissue. blood vessels & nervous tissue. TerminologyTerminology: myo : myo & sacro. & sacro. FunctionsFunctions: movement, maintain posture, : movement, maintain posture, stabilize joints & temperature homeostasis.stabilize joints & temperature homeostasis.

Individual Individual fibersfibers surrounded by surrounded by endomysiumendomysium (areolar connective tissue), multiple fibers bundled (areolar connective tissue), multiple fibers bundled as as fasciclesfascicles, fascicles bound by collagen sheath , fascicles bound by collagen sheath ((perimysiumperimysium), ), epimysiumepimysium surrounds all fascicles, surrounds all fascicles, deep fasciadeep fascia binds binds musclesmuscles into functional groups into functional groups

SarcolemmaSarcolemma (plasma membrane), (plasma membrane), sarcoplasmsarcoplasm (cyt- (cyt-oplasm of muscle cells), oplasm of muscle cells), myofibrilsmyofibrils (contractile (contractile elements of skm), elements of skm), A-band A-band (dark band): anisotropic (dark band): anisotropic (polarize light), (polarize light), I-bandI-band (light band): Isotropic(non- (light band): Isotropic(non-polarizing), polarizing), H-bandH-band (within A-band): visible only (within A-band): visible only in relaxed muscle, in relaxed muscle, M-lineM-line (bisects H-band), (bisects H-band), Z-discZ-disc (membrane): midline in I-band, (membrane): midline in I-band, SarcomereSarcomere (region (region between two successive Z-discs): functional unitbetween two successive Z-discs): functional unit

MicrofilamentsMicrofilaments (myofilaments) with in bands (myofilaments) with in bandsThick filaments (myosin)Thick filaments (myosin): entire length of A-band, : entire length of A-band, thin filaments (actin)thin filaments (actin): across I-band & part of A-: across I-band & part of A-band, band, Z-discZ-disc (protein sheet connecting myofibrils) (protein sheet connecting myofibrils)

Thick filamentsThick filaments: Myosin, rodlike tail terminates in : Myosin, rodlike tail terminates in two globular heads, tail two globular heads, tail consistsconsists ofof heavy meromysin heavy meromysin(polypeptide chains (2) interwoven), head consists (polypeptide chains (2) interwoven), head consists of ends of heavy meromysin + light meromysin, of ends of heavy meromysin + light meromysin, during contraction heads (cross bridges) interact during contraction heads (cross bridges) interact with thin myofilaments, with thin myofilaments, thin myofilamentsthin myofilaments: actin, : actin, consists of G (globular) actin, double stranded helixconsists of G (globular) actin, double stranded helixregulatory proteinsregulatory proteins: tropomyosin, sprial around : tropomyosin, sprial around actin, block myosin head binding sites: relaxation, actin, block myosin head binding sites: relaxation, troponin (polypeptide complex), binds Catroponin (polypeptide complex), binds Ca2+2+ (TnC), (TnC), binds tropomyosin (TnT) & binds actin (TnI)binds tropomyosin (TnT) & binds actin (TnI)

Contraction of skeletal muscle (sliding theory)Contraction of skeletal muscle (sliding theory): : Thin filaments slide past thick ones, overlap to a Thin filaments slide past thick ones, overlap to a greater degree. Prior to contraction cross bridges greater degree. Prior to contraction cross bridges are disengaged & all bands distinct. Nerve impulse are disengaged & all bands distinct. Nerve impulse initiates contraction, cross bridges engage, ATP initiates contraction, cross bridges engage, ATP splits, energy used for swinging of cross bridges, splits, energy used for swinging of cross bridges, actin filaments pulled together, H-zone and Z-disc actin filaments pulled together, H-zone and Z-disc smaller or lost, I-band reduced, cross bridges smaller or lost, I-band reduced, cross bridges disengage & filaments return to original position.disengage & filaments return to original position.

During relaxed stateDuring relaxed state: Ca: Ca2+2+ conc. in sarcoplasm is conc. in sarcoplasm is low (stored in SR), troponin-tropomyosin complex low (stored in SR), troponin-tropomyosin complex attached to actin filament (to block myosin binding attached to actin filament (to block myosin binding sites on actin filament), ATP and inactive ATPase sites on actin filament), ATP and inactive ATPase bound to myosin head (low energy configuration, bound to myosin head (low energy configuration, binding to actin not possible)binding to actin not possible)

Events during contractionEvents during contraction: Nerve impulse (afferent : Nerve impulse (afferent signal) from motor neuron generates AP in nerve signal) from motor neuron generates AP in nerve cell, AP propagated along sarcolemma and down T cell, AP propagated along sarcolemma and down T tubules, myosin ATPase activated (ATP splits to tubules, myosin ATPase activated (ATP splits to high energy myosin-ADP complex), AP causes high energy myosin-ADP complex), AP causes release of Carelease of Ca2+2+ from SR, binds to troponin, from SR, binds to troponin, molecular shape of troponin changes (tropomyosin molecular shape of troponin changes (tropomyosin is removed from binding site of mysosin on the is removed from binding site of mysosin on the actin filament), myosin attaches to actin. actin filament), myosin attaches to actin.

ContractionContraction: potential energy stored in high-: potential energy stored in high-energy configuration is used to pivot myosin head energy configuration is used to pivot myosin head (myosin head bends as it pulls on actin, ADP and (myosin head bends as it pulls on actin, ADP and inorganic phosphate are released from myosin), inorganic phosphate are released from myosin), new ATP attach to myosin head (cross bridge new ATP attach to myosin head (cross bridge simultaneously detach), following death no ATP simultaneously detach), following death no ATP (muscle cannot relax: rigor mortis), if no new (muscle cannot relax: rigor mortis), if no new impulse; Caimpulse; Ca2+2+ is pumped back into (SR), relaxation is pumped back into (SR), relaxation occurs, if Caoccurs, if Ca2+2+ present from additional impulse; present from additional impulse; cycle repeats (myosin head “steps” to next binding cycle repeats (myosin head “steps” to next binding site on actin)site on actin)

BASIM ZWAIN LECTURE NOTESBASIM ZWAIN LECTURE NOTES

MuscleMuscle

ExitExit HomeHome

Regulation of ContractionRegulation of Contraction

Neuromuscular junctionNeuromuscular junction isis connection between connection between somatic nervous system and musclessomatic nervous system and muscles: motor neuron : motor neuron axons bifurcate to form multiple endings: separate axons bifurcate to form multiple endings: separate endings synapse with individual mfs (mf synapses endings synapse with individual mfs (mf synapses with single motor neuron, motor neurons synapse with single motor neuron, motor neurons synapse with multiple mf)with multiple mf)

SynapseSynapse is site of communication between neuron is site of communication between neuron and muscleand muscle (neuron to neuron in nervous system): (neuron to neuron in nervous system): Contact is not direct, physical separation, synaptic Contact is not direct, physical separation, synaptic cleft, requires signal, transduced to chemical signalcleft, requires signal, transduced to chemical signal(NT, ACh is NT at NMJ)(NT, ACh is NT at NMJ)Motor end plate is physical modification of sarco-Motor end plate is physical modification of sarco-lemmalemma where neuron synapses with fiber, ACh where neuron synapses with fiber, ACh receptors located on motor end platereceptors located on motor end plate

Transduction eventsTransduction events::1.1. Nerve impulse, Nerve impulse, 2.2. ACh released from presynaptic ACh released from presynaptic motor neuron, motor neuron, 3.3. Binds to receptors, Na Binds to receptors, Na++ channels channels open, depolarizing current, AP, ACh destroyed open, depolarizing current, AP, ACh destroyed (ACE), (ACE), 4.4. AP propagated, sarcolemma, T tubules, AP propagated, sarcolemma, T tubules, 5.5. Ca Ca2+2+ released from SR, released from SR, 6.6. Ca Ca2+2+ removed by Ca removed by Ca2+2+ pumps, contraction ceases, pumps, contraction ceases, 7.7. At individual muscle At individual muscle fibers (cells); contraction is all or nothing, in fibers (cells); contraction is all or nothing, in response to threshold stimuli, APs are generated in response to threshold stimuli, APs are generated in a non-graded fashion, a non-graded fashion, 8.8. Refractory period cells Refractory period cells must re-polarize before another APmust re-polarize before another AP

Motor unit Motor unit

Could be small in size (few collaterals arise from Could be small in size (few collaterals arise from motor nerve to supply few muscle fibers) or large motor nerve to supply few muscle fibers) or large in size (so numerous collaterals and muscle fibers). in size (so numerous collaterals and muscle fibers). Three types of muscle fibers: Three types of muscle fibers: Slow oxidativeSlow oxidative fibers fibers (slow red), (slow red), fast oxidativefast oxidative fibers (fast red) which is fibers (fast red) which is very rare in human, very rare in human, fast glycolyticfast glycolytic fibers (fast fibers (fast white). Skeletal muscle is a mixture of these types white). Skeletal muscle is a mixture of these types of fibers, so there are red and white musclesof fibers, so there are red and white muscles

Red musclesRed muscles contain higher % of red fibers with contain higher % of red fibers with few white fibers. They respond slowly, long latency, few white fibers. They respond slowly, long latency, specialized for posture maintenance, contain more specialized for posture maintenance, contain more blood capillaries, mitochondria and myoglobin, blood capillaries, mitochondria and myoglobin, resistant to fatigue, sensitive to hypoxia. resistant to fatigue, sensitive to hypoxia. White White musclesmuscles contain higher % of white fibers, few red contain higher % of white fibers, few red fibers, respond quickly, short latency, specialized fibers, respond quickly, short latency, specialized for fine skilled movements, less blood capillaries, for fine skilled movements, less blood capillaries, mitochondria and myoglobin, less sensitive to mitochondria and myoglobin, less sensitive to hypoxia, easily fatigued. When nerve to slow fiber hypoxia, easily fatigued. When nerve to slow fiber replaced by nerve to fast fiber; slow becomes fast! replaced by nerve to fast fiber; slow becomes fast!

Muscle twitchMuscle twitch: response of muscle to single supra-: response of muscle to single supra-threshold stimulus, 3 Phases: threshold stimulus, 3 Phases: latent phaselatent phase (few ms), (few ms),contraction phasecontraction phase ( (10-10010-100 ms), ms), relaxationrelaxation((10-10010-100 ms) ms) Graded responses depend on stimulation frequency Graded responses depend on stimulation frequency & strength. Temporal (wave) summation: strength & strength. Temporal (wave) summation: strength of contraction increases with successive stimuli, of contraction increases with successive stimuli, fibers that are already contracted, contract further fibers that are already contracted, contract further with additional Cawith additional Ca2+2+, if stimulation is delivered , if stimulation is delivered prior to relaxation, contractions are summedprior to relaxation, contractions are summed

TetanusTetanus: At high frequencies, no relaxation occurs, : At high frequencies, no relaxation occurs, contractions fuse, smooth sustained contractioncontractions fuse, smooth sustained contractionMotor unit summationMotor unit summation (response to ncrz stimulus (response to ncrz stimulus intensity): primary mechanism for ncrz force of intensity): primary mechanism for ncrz force of contraction, multiple motor unit summation contraction, multiple motor unit summation (recruitment), at threshold; first contraction, as (recruitment), at threshold; first contraction, as stimulus intensity ncrz; additional units activated, stimulus intensity ncrz; additional units activated, maximal stimulus: strongest, causes ncrz contract-maximal stimulus: strongest, causes ncrz contract-ion, accomplished by ncrz neural activationion, accomplished by ncrz neural activation

TreppeTreppe force of contraction ncrz during response force of contraction ncrz during response to stimuli at the same strength, result of ncrz Cato stimuli at the same strength, result of ncrz Ca2+2+ availability, heat created during contraction ncrz availability, heat created during contraction ncrz efficiency of enzymes (warming, athletic activity)efficiency of enzymes (warming, athletic activity)

Isotonic and Isometric contractionsIsotonic and Isometric contractionsTensionTension is force of contracting muscle on an object, is force of contracting muscle on an object, loadload is reciprocal force exerted by object, to move is reciprocal force exerted by object, to move object; tension must be greater than load.object; tension must be greater than load.Isotonic contractionIsotonic contraction (change in length): (change in length): concentricconcentric (muscle shortens and does work), (muscle shortens and does work), eccentriceccentric (muscle (muscle contracts as it lengthens), concentric and eccentric contracts as it lengthens), concentric and eccentric can occur at the same time, eccentric put muscle to can occur at the same time, eccentric put muscle to concentric, concentric, isometric contractionisometric contraction (tension ncrz but (tension ncrz but length constant): load greater than force (mainten-length constant): load greater than force (mainten-ance of posture, most movements involve bothance of posture, most movements involve both

Muscle Metabolism Muscle Metabolism ATP is sole source of energy ATP is sole source of energy for contraction, little for contraction, little ATPATP is stored, regenerated is stored, regenerated (recycled) rapidly: (recycled) rapidly: direct phosphorylationdirect phosphorylation of ADP of ADP by creatine phosphate, by creatine phosphate, anaerobic glycolysisanaerobic glycolysis (in the (in the absence of Oabsence of O22, glycolytic products “pyruvic acid” , glycolytic products “pyruvic acid”

are metabolized to lactic acid producing additional are metabolized to lactic acid producing additional small quantities of ATP, small quantities of ATP, aerobic respirationaerobic respiration: 95% : 95% of ATP during light exercise, in presence of Oof ATP during light exercise, in presence of O22, ,

products of glycolysis broken down entirely, with products of glycolysis broken down entirely, with generation of large amounts of ATP, glycogen is generation of large amounts of ATP, glycogen is the source of glucose for both aerobic & anaerobicthe source of glucose for both aerobic & anaerobic

Fatty acids are the major source of energy at restFatty acids are the major source of energy at restForce of Contraction Force of Contraction more motor units recruited; more motor units recruited; greater force, greater cross sectional area; greater greater force, greater cross sectional area; greater tension, optimum resting length is the length at tension, optimum resting length is the length at which maximum force can be generatedwhich maximum force can be generated

Velocity and duration of contraction l Velocity and duration of contraction l as load ncrz, as load ncrz, velocity and duration decrease, muscle fiber type velocity and duration decrease, muscle fiber type (slow or fast), pathway for ATP formation (aerobic (slow or fast), pathway for ATP formation (aerobic or anaerobic glycolysis)or anaerobic glycolysis)

Cardiac MuscleCardiac Muscle

Branched, interdigitated, syncytium, intercalated Branched, interdigitated, syncytium, intercalated discs, gap junctions, RMP = -85 mV, AP slow, discs, gap junctions, RMP = -85 mV, AP slow, plateau, AP phases are: plateau, AP phases are: Phase 0Phase 0: Depolarization: 2 : Depolarization: 2 ms, activation of all Nams, activation of all Na++ channels, influx of Na channels, influx of Na+, +,

Phase 1Phase 1: Initial rapid repolarization, inactivation of : Initial rapid repolarization, inactivation of NaNa++ channels, channels, Phase 2Phase 2: Plateau: 200 ms, opening of : Plateau: 200 ms, opening of CaCa2+2+ channels, influx of Ca channels, influx of Ca2+, 2+, Phase 3Phase 3: Late rapid : Late rapid repolarization, closure of Carepolarization, closure of Ca2+2+ channels, channels, Phase 4Phase 4: : Base line (RMP)Base line (RMP)

mV +20 0 _ 85 0 Time >200 ms

0

2 1

3

4

Pacemaker potential: Cardiac muscle contraction Pacemaker potential: Cardiac muscle contraction myogenicmyogenic, (originated in muscle) not , (originated in muscle) not neurogenicneurogenic (initiated by nerve), nerve is (initiated by nerve), nerve is regulatoryregulatory: presence : presence of specialized conductive tissue in heart, of specialized conductive tissue in heart, pacemaker tissue, unstable low potential, pacemaker tissue, unstable low potential, prepotentialprepotential, declines & depolarizes continuously: , declines & depolarizes continuously: decrease in Kdecrease in K++ efflux, spreads impulses all over efflux, spreads impulses all over heart. Steeper prepotent-ials: heart. Steeper prepotent-ials: tachycardiatachycardia, lower , lower prepotentials: prepotentials: bradycardiabradycardia..

Prepotentials NNoorrmmaall rrhhyytthhmm BBrraaddyyccaarrddiiaa TTaacchhyyccaarrddiiaa

Smooth muscleSmooth muscle

Small, spindle-shaped, sheets of opposing fibers, Small, spindle-shaped, sheets of opposing fibers, generally two sheets (longitudinal & circular): generally two sheets (longitudinal & circular): peristalsis, lacks highly structured NMJ, lower peristalsis, lacks highly structured NMJ, lower myosin to actin ratio than skm (1:13 vs. 1:2), lacks myosin to actin ratio than skm (1:13 vs. 1:2), lacks troponin complex and sarcomeres. Gap junctions troponin complex and sarcomeres. Gap junctions make entire sheet responds to a single stimulus, make entire sheet responds to a single stimulus, some has pacemaker, some self-excitatory, Casome has pacemaker, some self-excitatory, Ca2+ 2+

interacts with regulatory molecules: calmodulin, interacts with regulatory molecules: calmodulin, slow, sustained & resistant to fatigue. It contracts slow, sustained & resistant to fatigue. It contracts in response to stretch.in response to stretch.

Property of stress-relaxation (plasticity)Property of stress-relaxation (plasticity) , gradual , gradual increase in stretch; tension increase then decrease increase in stretch; tension increase then decrease even below its initial level, uterus to adapt increase even below its initial level, uterus to adapt increase in fetal size, urinary bladder to adapt increase in in fetal size, urinary bladder to adapt increase in urine volume. Sm in continuous partial contraction urine volume. Sm in continuous partial contraction (tone), nerve supply & multiple NT to modify tone, (tone), nerve supply & multiple NT to modify tone, also affected by chemicals, pH, temperature, COalso affected by chemicals, pH, temperature, CO22, ,

OO22 ....etc, Two types of sm: ....etc, Two types of sm: Single-unit Single-unit && Multi-unit Multi-unit

Single-unit smooth muscle: Single-unit smooth muscle: Function as syncytium, Function as syncytium, found mainly in the wall of hollow viscera. found mainly in the wall of hollow viscera. Multi-unit smooth muscle: Multi-unit smooth muscle: No gap junctions, each No gap junctions, each muscle works individually, found in the iris of eye, muscle works individually, found in the iris of eye, vas deferens, epididymus, large pulmonary airways vas deferens, epididymus, large pulmonary airways and large blood vessels. They have many functional and large blood vessels. They have many functional similarities to skeletal muscles but irregularly and similarities to skeletal muscles but irregularly and involuntarily contract with prolonged duration. involuntarily contract with prolonged duration.

Comparison of skeletal, cardiac & smooth muscleComparison of skeletal, cardiac & smooth muscleCharacteristic Skeletal Cardiac Smooth Location Attached to

bones, fascia and skin

Walls of heart Single-unit: visceral organs Multi-unit: Internal eye muscles, large airways and arteries

Appearance Single, long, cylindrical, striated, multinucleate

Branching chains of cells, uninucleate, striated

Single, non-striated, uninucleate

Connective Tissue

Epimysium, perimysium, endomysium

Endomysium Endomysium

Sarcomere Present Present None T Tubules Present at each

end Present at one end

None

Characteristic Skeletal Cardiac Smooth Gap Junctions None Intercalated

discs In single-unit

Neuromuscular Junctions

Present None In multiunit

Regulation of Contraction

Somatic NS; voluntary

Autonomic NS, intrinsic (pacemaker), hormones, involuntary

Autonomic NS, hormones, local regulation, response to stretch

Ca2+ Source SR SR, extracellular fluid

SR, extracellular fluid

Role of Ca2+ Via troponin/actin interactions

Via troponin/actin interactions

Via calmodulin/myosin interaction

Characteristic Skeletal Cardiac Smooth Pacemakers None Present In single-unit Nervous System Affects

Excitation Excitation or inhibition

Excitation or inhibition

Speed of Contraction

Varies: slow to fast

Slow Very slow

Rhythmic Contraction

None Yes In single-unit

Response to Stretch

Strength of contraction increases

Strength of contraction increases

Stress-relaxation response (plasticity)

Respiration Aerobic or anaerobic

Aerobic Primarily anaerobic

BASIM ZWAIN LECTURE NOTESBASIM ZWAIN LECTURE NOTES

MuscleMuscle

ExitExit HomeHome

Muscle MechanicsMuscle MechanicsLever systems