Lecture 12, 07 Oct 2003Chapter 10MusclesVertebrate PhysiologyECOL 437University of ArizonaFall 2003instr: Kevin Boninet.a.: Bret PaschVertebrate Physiology 4371. Muscle Contraction (Ch10)2. Announcements3. RabbitsA non-FridayseminarUses: - most observable animal behavior - most visceral function - generally act by shorteningMuscleClassification: - striated - smooth skeletal or cardiacAll muscle movement based onmyofilaments (actin and myosin)sliding past each other…Utilize: ATP, Ca2+, ~APs walls of hollow organs(Myo-, Sarco- = muscle related )Structure:Skeletal Muscle - muscle attached to bone (skeleton) via tendons - muscle comprises elongate, multinucleate, muscle fibers - multinucleate muscle fibers derived from combination of many myoblasts (embryonic muscle cells) - within each muscle fiber are many parallel myofibrils - each myofibril contains sarcomeres arranged in series (end-to-end) - sarcomere is functional unit of muscleSarcomereZ-disk at eachend of sarcomereSarcomeres in adjacent myofibrils are aligned leadingto striated appearanceActin thin myofilamentsattached to each Z-diskMyosin thickmyofilaments inbetween actins (6,3)Actin and Myosinoverlap is what allowsmuscle contraction(6,3)SarcomereZ-disk (actin attaches)Areas within sarcomere given names:I-band (actin only)A-band (myosin length)H-zone (myosin only)M-line (midpoint ofmyosin)During muscle contraction,myosin thick filaments slidepast actin thin filamentstoward Z-linesWhich regions change length and which remain thesame as the sarcomere shortens?Z-disk (actin attaches)I-band (actin only)A-band (myosin length)H-zone (myosin only)M-line (midpoint ofmyosin)During muscle contraction,myosin thick filaments slidepast actin thin filamentstoward Z-linesSarcomere CompositionActin composed of:individual molecules of G-actin (globular)united into chains called F-actin (filamentous)which form a two-stranded helixIn the groove of the two F-actin strands is tropomyosin,which also has globular troponin molecules attached to itSarcomere CompositionMyosin composed of: 2 heavy chains with globular heads 2 essential light chains 2 regulatory light chainsMyosin molecules spontaneouslyaggregate into complexes withthe heads at the ends and thetails toward the middleThe light chains are involvedin the speed of contraction(important for differentmuscle fiber-types)Sarcomere FunctionCross-bridges formtransiently betweenmyosin head andactin filament(actomyosin)Actin and Myosin molecules slide past each other, but don’tthemselves change lengthSarcomere shortensduring contractionSliding Filament TheoryCross Bridges and Force ProductionMyosin head binds to actin (actomyosin), then pullsmyosin toward z-line thereby shortening sarcomere(= contraction)Vander et al., 2001Cross-bridge forces are additive.Same force all along myofibril.Sarcomere FunctionNumber of Cross-bridges (and thereforecontraction magnitude)increased withappropriate overlap ofactin with myosin headsLength-TensionRelationshipNormal muscle function at ornear the plateau (1.8-2.2)Length-TensionRelationshipWhy lose force production atshort end?What constrains muscle lengthin the body?Vander et al., 2001Myosin head has to be able to detachand bind again to actin further alongin order to continue to generate forceDetachment requires ATP bind tomyosin headVander et al., 2001Cross Bridges and Force ProductionATP required for the (3)dissociation of actin andmyosin (else rigor mortis)Myosin acts as anATPase, hydrolyzing ATPto ADP + Pi (4 -> 1)Energy of ATPhydrolysis “cocks” themyosin head (4)Myosin releases ADPand Pi (very slowly (2)unless bound to actin)Regulation of ContractionCALCIUM and the cross bridgeNeed free Ca2+ in cytosolto get contractionCalcium binds troponinwhich is attached totropomyosin on actinThis causes conformationalchange in tropomyosin exposingactin binding sites for myosinheads (not shown)Without calcium,contraction is inhibitedVander et al., 2001Excitation-Contraction CouplingHow an AP in muscle plasma membrane leads ultimately tochanges in intracellular [Ca2+], and therefore contractionArtificially change membrane potential.In reality, most AP’s lead to all-or-noneresponse of muscle (-90mV -> +50mV)Excitation-Contraction Coupling, from the beginning…1. AP from CNS arrives atneuromuscular junction.2. ACh released into synapse.3. ACh binds to nicotinicreceptors on motor endplate.4. Ion channels for K+ and Na+open; greater Na+ influx leadsto depolarization and AP inmuscle plasma membraneEPP = Endplate Potential(~Excitatory Post-Synaptic Potentialor EPSP)Excitation-Contraction Coupling, the middle I…5. Change in membranepotential (AP) reaches deepinto the muscle cell viatransverse tubules (T-tubules;one per Z-disk)Excitation-Contraction Coupling, the middle II…6. T-tubules have voltagesensitive proteins calleddihydropyridine receptors8. Calcium stored in the SR. Released into the cytosol viathe ryanodine receptor channel when the RR is mechanicallytriggered by the voltage sensitive dihydropyridine receptor.7. Dihydropyridine receptors in theT-tubules are mechanically linkedwith ryanodine receptors (RR) onthe sarcoplasmic reticulum (SR)The ends of the SR adjacent to the T-tubule arecalled terminal cisternae (w/ calsequestrin)Excitation-Contraction Coupling, the last bit…9. Calcium triggers release of more calcium from someryanodine receptors that are not linked todihydropyridine receptors10. Calcium binds to troponin leading to actomyosin complex…Called calcium-induced calcium release11. After repolarization, calcium actively (requires ATP) movedback into SR where much of it is bound to calsequestrin12. Muscle relaxes as long as ATP is present to allowactomyosin complex to dissociateTime course of excitation-contraction eventsLatent period about 2msSherwood, 1997Review of ECCoupling andMuscleContraction(Also a nicesummary onp. 387 ofyour