Skeletal Muscle Physiology - MBBS Stage 1 PDF

MBBS Stage 1 Skeletal Muscles Dr Kosha Mehta [email protected] Content of learning By the end of this session, you should be able to describe: Structure of skeletal muscle and muscle fibres Initiation of action potential at the NMJ and the principal ion channels involved...

MBBS Stage 1 Skeletal Muscles Dr Kosha Mehta [email protected] Content of learning By the end of this session, you should be able to describe: Structure of skeletal muscle and muscle fibres Initiation of action potential at the NMJ and the principal ion channels involved Roles of the action potential and sarcoplasmic reticulum in regulating intracellular Ca2+ concentration Myofilaments and how intracellular Ca2+ concentration controls the cross-bridge cycle that gives rise to contraction Length-tension relationship and its consequences for muscle function Slow and fast twitch skeletal muscle fibres Structure of skeletal muscle and muscle fibres 3 types of muscles 1. Skeletal muscles 2. Cardiac muscles 3. Smooth muscles  Skeletal muscle-location and structure Nucleus Muscle fibre (cell) Striations Skeletal muscle fibres: Large cells Multinucleated cells Appear striped or striated https://www.researchgate.net/figure/Unveiled-human-body-Illustration-of-the-main-skeletal-muscles-constitutive-of- the_fig2_326683494 Skeletal muscle- structure Human Physiology –An integrated Approach 6th Edition (Pearson)  Structure of muscle fibre (muscle cell) Mitochondria Sarcoplasmic reticulum Thick Thin Nucleus filament filament (Myosin) (Actin) T-tubules Myofibril Sarcolemma Human Physiology –An integrated Approach 6th Edition (Pearson)  Structure of muscle fibre. Sarcolemma Myofibril Z-line Sarcomere: between H-band two Z lines Z-line Triad T-tubule Terminal cisterna of Human Physiology –An integrated Approach 6th Edition (Pearson) sarcoplasmic reticulum  T-tubules and sarcoplasmic reticulum T-tubule brings action potentials Sarcoplasmic into the interior of muscle fibre reticulum stores Ca2+ Sarcolemma Human Physiology –An integrated Approach 6th Edition (Pearson)  I band Myofibril structure I band H zone Sarcomere: between two Z lines A band (red) Z line Z line M line Thick filament (myosin) Thin filament (actin) Human Physiology –An integrated Approach 6th Edition (Pearson) Initiation of action potential at the NMJ Principal ion channels involved Excitation-contraction coupling Muscle contractile cycle Skeletal muscle- Phase 1: innervation and excitation Slide X Ach= acetylcholine Human Physiology –An integrated Approach 6th Edition (Pearson) Skeletal muscle- Phase 1: innervation and excitation Neuromuscular transmission- depolarisation block Slide Y Ach Na+ Na+ Voltage-gated sodium channel -allows selective entry of Na, opened by Ach receptor voltage alteration -90 mV -50 mV +10 mV Non-selective ion channel, brief EPP event Small depolarization (action potential) receptor-gated channel i.e. opens upon activation of receptor? K+ contraction Ca2+ Slide Courtesy: Dr Phil Aronson  Initiation of muscle action potential Skeletal muscle- Phase 1: innervation and excitation Slide Z DHP=dihydropyridine receptor RyR=ryanodine receptors, the SR Ca2+ release channels Human Physiology –An integrated Approach 6th Edition (Pearson) Skeletal muscle- Phase 2: excitation-contraction coupling Sarcoplasmic DHP receptor reticulum (SR) Myosin thick filament Human Physiology –An integrated Approach 6th Edition (Pearson) DHP and Ryanodine receptors J Clin Invest DOI: 10.1172/JCI25525  Skeletal muscle- Phase 3: relaxation. Human Physiology –An integrated Approach 6th Edition (Pearson) Calcium Signals (free cytosolic Ca ions) initiate contraction Troponin Actin Tropomyosin moves, exposes myosin binding site on actin Myosin head Tropomyosin Actin moves Power stroke Relaxed state Myosin head “cocked” Initiation of contraction Tropomyosin partially blocks A Ca signal initiates contraction myosin binding site on actin Myosin weakly bound to actin Troponin controls positioning of tropomyosin Human Physiology –An integrated Approach 6th Edition (Pearson)  Skeletal Tight binding in the rigor state muscle- contractile ATP binds to myosin cycle head, myosin releases actin End of the power stroke- myosin Myosin hydrolyses undergoes ATP conformational ADP and Pi change, remain in myosin myosin head head releases ADP Energy released Calcium signal rotates myosin initiates head to cocked Power stroke position begins when Now myosin is tropomyosin move weakly bound to Human Physiology –An integrated off binding site actin Approach 6th Edition (Pearson)  Skeletal muscle- functionality How is movement/force mediated? Signal to initiate muscle contraction = calcium signal Movement is created when a motor protein myosin uses energy from ATP to change its conformation. https://www.youtube.com/watch?v=BVcgO4p88AA Action Potential and Twitch Length-tension relationship  Duration of Action Potential and Twitch (contraction) Action Potential is significantly shorter than the twitch time Muscle When several action potentials occur Twitch before the initial twitch cycle is complete, twitches superimpose on each other; a process called summation Summation occurs when -the frequency of twitch > rate at which calcium can be Contraction removed Latent Relaxation period period period Calcium removal is necessary for muscle Ca++ ions in sarcoplasm Tension decreases as relaxation, AP causes bound to troponin, contraction stops. Ca+ therefore, muscle cannot relax fully Ca++ release cross-bridges formed, + ions are pumped out of from SR, no between twitches sarcomeres are sarcoplasm into SR, cross- contraction actively shortening to bridge cycling stops, If this happens, increased cytosolic yet the point of peak muscle fibres return to calcium exposes more myosin binding tension resting state sites on actin…> more cross-bridges ….>  Length-tension relationship and its consequences for muscle function The tension a muscle can generate is related to the number of cross-bridges formed between the thick and thin filaments. Contraction means shortening of the sarcomere, overlap of thick and thin filaments. Max tension As the sarcomere shortens generated (C), (D) more crossbridges form optimal overlap (C) and the force increases until the crossbridges reach the Z disc. Beyond this there are lesser new binding sites (B) and therefore the tension Drop in Drop in decreases rapidly (A). tension tension Sarcomere shortens too much, In an elongated fibre (increased part of actin is not bound to sarcomere length) there are very myosin, as no myosin in centre of few crossbridges (E), therefore Human Physiology –An integrated sarcomere Approach 6th Edition (Pearson) little power can be generated.  Slow and fast twitch skeletal muscle fibres  Slow and fast twitch skeletal muscle fibres. Skeletal muscles contain both types, but ratios can differ, Fast Twitch- depending on muscle function, Type 2 age, training etc. “Athletic performance is a complex trait that is influenced by both genetic and environmental factors” Slow twitch - Type 1  Slow and fast twitch skeletal muscle fibres Slow twitch muscle fibers (type-I) Fast Twitch muscle fibers (type-II) Larger sized fibers, produce greater and quicker force; Support quick, powerful movements such as sprinting or weightlifting; Lower concentrations of mitochondria and myoglobin; Contract quickly-Fatigue quickly, power for shorter durations, short-term contractions, metabolically efficient Type IIA fibers Type IIB fibers Produce less force and are slower to contract (intermediate muscle Produce the most force, but and produce maximal tension fibers- mix of type-I and inefficient (fatigue very fast) Produce sustained small movements Type IIB) due to low oxidative capacity, Maintain long-term contractions Able to use both and heavy reliance on Key for stabilization and postural control aerobic and anaerobic metabolism More mitochondria and myoglobin anaerobic energy Even fewer mitochondria Small muscle fibers surrounded by more systems than Type IIA capillaries Higher oxidative Fastest speed in developing This combination supports aerobic capacity, fatigue max tension metabolism and fatigue resistance for slower than type IIB prolonged submaximal (aerobic) exercise Intermediate speed activities in developing max Long distance endurance activities like tension marathon running  Summary of all chapters Skeletal muscle fibres are large, multinucleated, striped, with T tubules Sarcomere is the contractile unit Shortening of muscle involves rapid contraction cycles that move the thin filament along the thick filament Max tension is generated only upon optimal overlap of thick and thin filaments Excitation-contraction coupling: Acetylcholine is released from somatic motor neuron It initiates an action potential in muscle fibre Muscle action potential stimulates calcium release from SR Ion channels are involved in these steps Ca+2 combine with troponin and initiate contraction Action potential is significantly shorter than the twitch time 2 types of skeletal muscle fibres: Fast-twitch and slow-twitch Ratios can differ, depending on muscle function, age, training etc.