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Unformatted text preview: Muscle action potential
PSL302: Lecture 31, by Prof. MacKay" The action potential generated in muscle fibers is the same as in axons except that it has a longer Monday, about 5 ms. duration, Nov. 29, 2010 Action potentials travel from the NMJ to both ends of the fiber. Action potentials invade the `t-tubules', at regular intervals throughout the fiber. Muscle Contraction Muscle action potential - A.p. generated in muscle fibers is same as in axons, except that it has a longer duration - Voltage-gated Ca++ channels elongate a.p. duration - A.p.'s travel from NMJ to both ends of fiber via conduction thru membrane - Ap.'s invade the t-tubules, at regular intervals throughout the fiber (fusion of cells) Muscle Contraction - T-tubules: extensions from invaginations of external membrane into muscle fibre -> exits on other side - Distinguishing feature of muscle fibers: large bundles of myofibrils (contractile proteins inside muscle fibre) - T-tubules meander around myofibrils November 29, 2010 Excitation-contraction coupling Cisternae of the sarcoplasmic reticulum (SR) are apposed to the t-tubules. Depolarization of the t-tubules, molecularly triggers the opening of Ca++ channels in the sarcoplasmic reticulum. Each action potential triggers the release of a wave of Ca++ into the sarcoplasm.
November 29, 2010 - On either side of t-tubules is network of sarcoplasmic reticulum (SR): analogous to endoplasmic reticulum - Reservoir of Ca++ - Banding pattern of myofibrils: two types of protein filaments (thick + thin) - Overlap to create banding pattern Muscle Contraction - Thin = light, thick = dark - Lined up across many muscle fibers - Repeating pattern throughout fibre: one repeat is one sarcomere (~3m) - T-tubules line up w/ sarcomere at locations of overlap btwn thick + thin jxns Excitation-contraction coupling - Cisternae of sarcoplasmic reticulum (SR) are apposed to t-tubules - A.p.s invade t-tubules -> depolarization - Opens Ca++ channels in SR = influx of Ca++ into sarcoplasm = contraction - Each a.p. triggers release of wave of Ca++ channels in SR (found close to t-tubules) - Physical coupling btwn voltage-gated ion channels of t-tubules & Ca++ channels in SR Contractile proteins - Actin (thin) + myosin (thick) filaments: arranged in alternating, overlapping bands - Form sarcomere unit of myofibrils - Myosin in middle, actin on either side - Myosin: long chain + "head" portion - "Head" forms a cross-bridge when attached to binding sites on the actin molecule - At overlaps: "heads" stick out in every direction - Twd actin filament (and its binding site) - Binding sites for myosin spaced 36nm apart - Not found in middle of sarcomere: so actin filaments can be drawn twd center Contractile proteins Actin and myosin molecules are arranged in alternating, overlapping bands; form the sarcomere unit of myofibrils. The myosin `head' forms a cross-bridge when attached to binding sites on the actin molecule. The binding sites for myosin are spaced 36 nm apart. 2 3 1 of 4 PSL302: Lecture 31, by Prof. MacKay"
November 29, 2010 Exposing the binding site - At rest: myosin `head' can't bind to actin - Binding sites blocked by tropomyosin Muscle Contraction - A.p. comes: Ca++ binds to troponin (component of tropomyosin) - Causes tropomyosin to roll over - Exposes binding sites for myosin
troponin Monday, Nov. 29, 2010 Muscle Contraction November 29, 2010 Ca2+ bound Tropomyosin rolls over Binding sites g exposed Myosin binding site tropomyosin scle Cross-bridge formation - Myosin head fxns as ATPase Contraction - BUT only when bound to actin: knocks Pi off Cross-bridge (no hydrolysis rxn) - Not bound to actin: ADP + Pi attached to myosin headformation - When Ca++ is bound to troponin: myosin attachesmyosin head functions as an ATPase The to actin = becomes ATPase ATPase, but only when bound to = power stroke - Pi released from myosin head BUT leaves ADP boundactin. Exposing the binding sites bound - Power stroke uses stored elastic energy: When calcium isto actin.to troponin, the myosin attaches - Pi releases elastic energy: to Phosphate released, leaving p , At rest the myosin `head' cannot bind myosin drags actinisfilament g ADP bound head to the myosin head. - Noactin because the binding sites are blocked energy from ATP hydrolysis: myosin-actin cross-bridge is pre-energized Power = ADP + Pi attached - After power (tropomyosin). by another moleculestroke: ATP binds + hydrolyzes stroke uses stored elastic energy. = "cocked" Ca++ binds to troponin (a component of Pre-energized cross-bridge tropomyosin) and thereby exposes the binding sites for myosin by causing the tropomyosin to `roll over'. November 29, 201 Power Stroke
5 4 2 of 4 PSL302: Lecture 31, by Prof. MacKay" Monday, Nov. 29, 2010 - Resting state: myosin head (ADP+Pi) - Not bound to actin -> tropomyosin blocking - Ca++ influx, binds to troponin: myosin binds to actin - Tropomyosin rolls aside - Power stroke: Pi released - Elastic energy released - Myosin drags actin twd centre of sarcomere - Shorten overall sarcomere length - Post-power stroke: ATP replaces ADP - ATP binds more strongly to myosin head - Breaks myosin-actin cross-bridge - Hydrolysis = myosin head pre-energized - Cross-bridges operate asynchronously - When one in power stroke, another waiting for binding site to appear - 20% of myosin heads in power stroke - As soon as power stroke over, another myosin head takes up mvt = filament slides along Sliding filament model - Binding of myosin head pulls attached actin twd center of sarcomere ~10nm Muscle Contraction - Replacement of ADP by ATP on myosin head breaks cross-bridge link - Restores myosin head configuration - This action stores elastic energy in molecule Myosin reattachment - Myosin head cannot reattach to actin UNTIL it is opposite a binding site - B/c other cross-bridges in their power stroke, actin continues to slide along - Thus a binding site is soon available - As long as Ca++ remains bound to troponin, myosin heads reiterate mvt ++ removed by Ca++ ATPase pumps - Ca from sarcoplasm - Transport Ca++ into SR for storage - But as long as a.p.'s arrive, net Ca++ efflux out of SR = contraction - Shortening of sarcomeres shorten muscle fibre -> pull on tendons -> move limbs ATP supply - Myosin molecules are kept well supplied w/ ATP by adding a high-energy Pi to ADP from creatine phosphate (buffer to maintain ATP supplies) - Creatine (phospho)kinase (CK, or CPK): enzyme which transfers Pi - Located in centre of sarcomere: restore ATP lvls to muscle fibers ATP of ATP in - Creatine supplements endurance in muscles for athletes (higher lvls supply muscles) November 2 The myosin molecules are kept well supplied with ATP by adding a high-energy 3 of 4 phosphate to ADP from creatine phosphate. Creatine kinase (CK)--enzyme which transfers the phosphate--is located in the PSL302: Lecture 31, by Prof. MacKay" Monday, Nov. 29, 2010 Fatigue - Fatigue is not due to running out of ATP - Everything in body runs on ATP: if you run out, you're dead! - Most commonly, fatigue is caused by a breakdown in coupling btwn t-tubule depolarization & opening of SR Ca++ channels - Very sensitive to pH -> a.p.'s don't successfully open Ca++ channels - Breakdown due to acidity - Lactic acid (end pct of glycolysis) + free Pi (ATP hydrolysis) accumulation - Diff muscle fibers have diff rates of fatigue - Fast glycolytic fibers: anaerobic metabolism -> produce lactic acid = rapid fatigue - Slow oxidative fibers: aerobic metabolism -> produce little lactic acid = slow fatigue - As soon as fatigue sets in, less force produced by muscle fiber - NMJ driven harder: more a.p.s arrive! - But a.p.'s do less to release Ca++ from SR...until eventually nothing Termination of contraction - When m.u. impulses stop: no more Ca++ released from SR - Ca++ is actively pumped out of sarcoplasm by Ca++ ATPase pump back into SR - No Ca++ remains bound to troponin = no further cross-bridge formation Rigor mortis - In dead muscle tissue, Ca++ diffuses out into sarcoplasm - Ca++ ATPase pump no longer works - Myosin binds to every available actin site Muscle Contraction November 29, 2010 - No ATP is available, so myosin heads can't release from actin or be pre-energized - No contraction (actin sliding) occurs (no mvt = static) - Permanent cross-bridges btwn myosin & actin filaments = tissue stiffness Length-tension relationship - Density of cross-bridge formation is maximal for given overlap of actin + myosin filaments - Optimal overlap for maximal force at specific length of sarcomere, or of muscle - This muscle length (giving maximal force generation) corresponds to length at which muscle is used at high forces -> maximal potential for cross-bridge formation = maximal force Graph: force w.r.t. overlap - If muscle is too stretched, no overlap btwn filaments = no force - If muscle too contracted, actin filaments bunched at centre of sarcomere where no myosin heads are found = weak force November 29, 2010 - Include passive force + active force = total force (for good measure): muscle tissue is elastic - Use elasticity in mvts passively, i.e. running Muscle Contraction 4 of 4
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This note was uploaded on 03/27/2012 for the course PSL PSL300 taught by Professor Mackayfrench during the Fall '11 term at University of Toronto- Toronto.
- Fall '11