Muscle Physiology PDF

Learning Objectives By the end of this section, you should be able to: – Understand the process of excitation-contraction coupling – Describe the molecular interactions between the thick and thin filaments during cross-bridge cycling  Excitation-contractio...

Learning Objectives By the end of this section, you should be able to: – Understand the process of excitation-contraction coupling – Describe the molecular interactions between the thick and thin filaments during cross-bridge cycling  Excitation-contraction coupling Calcium initiates cross-bridge cycling after entering the cytoplasm. MODULE 4 – MUSCLE PHYSIOLOGY How? = Excitation-contraction coupling Action potential along the plasma membrane of a myofibre => many steps => triggers cross-bridge cycling Key pathway: Transverse tubule or T-tubule => directly links the plasma membrane and the lateral sacs. They run perpendicularly from the surface of the muscle cell membrane into the central portion of the muscle fibre. 126  Release of calcium from the sarcoplasmic reticulum Remember that the cytosolic calcium concentration is very low in a resting (relaxed) muscle! Action potential => Rapid increase in cytosolic calcium concentration. The source of increased calcium MODULE 4 – MUSCLE PHYSIOLOGY is the sarcoplasmic reticulum. Very similar to the endoplasmic reticulum => Forms sleeve-like segments around each myofibril. At the end of these segments = Lateral sacs => connected to each other via smaller tubular elements. A single t-tubule and 2 lateral sacs on either side forms the triad – key for excitation-contraction coupling 127 MODULE 4 – MUSCLE PHYSIOLOGY = voltage gated sensors Triad 128  The transverse tubules bring action potentials into the interior of the skeletal muscle fibres so that the wave of depolarization passes close to the sarcoplasmic reticulum T-tubule membrane contains voltage-sensitive Dihydropyridine receptors (DHPR) – activate in MODULE 4 – MUSCLE PHYSIOLOGY response to action potential travelling down t-tubule. DHPR are coupled to sarcoplasmic reticulum proteins, the ryanodine receptor (Ca2+ release channels) – activation leads to the release of calcium into the muscle cell The extensive meshwork of sarcoplasmic reticulum assures calcium can readily diffuse to all of the troponin sites. Activation 1. Action potential => T-tubule from the sarcoplasmic reticulum => Opening calcium channels. 2. Increase in cytosolic calcium concentration. 3. Calcium will bind to the subunit C (calcium) => Induces a change in the shape of the troponin. 4. Release of the inhibitory grip on tropomyosin. 5. Movement of tropomyosin making available myosin-binding sites. 6. Remove calcium from troponin => Reverses the process => Disconnects the cross bridge, relax 129 muscle.  MODULE 4 – MUSCLE PHYSIOLOGY 130  Passage of an action potential along the transverse tubule opens nearby voltage-gated calcium channels, the MODULE 4 – MUSCLE PHYSIOLOGY “ryanodine receptor,” located on the sarcoplasmic reticulum, and calcium ions released into the cytosol bind to troponin. The calcium-troponin complex “pulls” tropomyosin off the myosin-binding site of actin, thus allowing the binding of the cross-bridge, followed by its flexing to slide the actin filament. Calcium re-uptake into SR occurs through SERCA (SarcoEndoplasmic Reticulum Calcium ATPase) 131  MODULE 4 – MUSCLE PHYSIOLOGY 132  ATP-Powered cross-bridging cycling How does this start? Resting myofibre = low calcium concentration. No interaction between actin and myosin. MODULE 4 – MUSCLE PHYSIOLOGY Heads of myosin filament (M) are in an energized state resulting from ATP hydrolysis. The hydrolysis products (ADP and Pi) are both bound to the cross-bridge. M + ATP => M-ADP-Pi Calcium release => The myosin-binding site on actin becomes available, so the energized myosin heads bind and form a cross-bridge. M + ATP => M-ADP-Pi => Able to interact with Actin (if tropomyosin removed) 133 MODULE 4 – MUSCLE PHYSIOLOGY M + ATP => M-ADP-Pi Binding A-M.ADP.Pi Power stroke = Movement of the cross-bridge Release of ADP+Pi The full hydrolysis and departure of ADP + Pi causes the flexing of the bound cross-bridge. 134  Hydrolysis of the bound ATP energizes or “re-cocks” the bridge. MODULE 4 – MUSCLE PHYSIOLOGY Binding of a “new” ATP to the cross- bridge uncouples the bridge. 135  MODULE 4 – MUSCLE PHYSIOLOGY 136  ATP plays an important role for skeletal muscle contraction MODULE 4 – MUSCLE PHYSIOLOGY Rigor mortis 137 Learning Objectives By the end of this section, you should be able to: – Describe the structure and function of a motor unit and their classification – Understand the generation and control of skeletal muscle force – Explain the interactions between muscle structure and load on contraction output  Skeletal muscle contractile activity An action potential lasts 1-2 msec in a myofiber MODULE 4 – MUSCLE PHYSIOLOGY and no mechanical activity is observable before it ends. Mechanical activity: About 100 ms. The latent period between excitation and development of tension in a skeletal muscle includes the time needed to release Ca2+ from sarcoplasmic reticulum, move tropomyosin, and cycle the cross-bridges... Notions of contraction time, relaxation time, muscle twitch. 138  Skeletal muscle mechanics: Contraction of the whole muscle A single action potential in a muscle fibre => brief and weak contraction = Twitch. MODULE 4 – MUSCLE PHYSIOLOGY A twitch is too weak and too short to have a real effect at the level of the entire muscle and the body. => Muscle fibres cooperate to produce muscle contractions for variable strength...that’s why you can vary the force developed by your muscles. How? 1) By changing the number of fibres contracting (recruited) within the muscle. 2) By affecting the tension developed by each contracting fibre (i.e., activation rate). Motor unit = one motorneuron + all the myofibres it innervates (different size depending on muscle types). Upon reaching a muscle, the axon makes several divisions/branches, and each branch will form one connection with one fibre = Neuromuscular junction. Motor unit recruitment – all muscle fibres within a motor unit are activated when a motor unit is recruited => The greater the number of motor units recruited to contract, the greater the total muscle tension! 139  MODULE 4 – MUSCLE PHYSIOLOGY 140  Different muscles can have different numbers and sizes of motor units to vary the power and dexterity of movement MODULE 4 – MUSCLE PHYSIOLOGY Fingers: less fibres per motor unit = greater control of fine movements Back muscles: more fibres per motor unit = less control of fine movements Notion of asynchronous recruitment of motor units and fatigue prevention. Muscles are often composed of different fibre types => More (Type I) or less (Type II) resistant to fatigue. Weak or moderate exercise => Recruitment of motor units more resistant to fatigue first (Type I). 141  How do we determine which motor units to recruit? Henneman’s size principle – describes the relationship between the size of a motor unit and its sequence of recruitment (i.e., when it first MODULE 4 – MUSCLE PHYSIOLOGY begins to discharge action potentials) In other words, motor units are recruited according to the magnitude of their force output, from smallest to largest Benefits of orderly recruitment of motor units: Minimizes fatigue by first activating fatigue-resistant (i.e., type I) muscle fibres. - larger, more powerful units are recruited when more force is needed Allows the finer control of muscle forces - weaker units allows smaller gradation of force during low-level contractions Simplifies the control of force - central nervous system is not burden by determining which motor units to activate (occurs automatically according to size of motor neuron) 142  Frequency of activation Whole muscle tension => Number of fibres contracting (i.e., motor unit recruitment) and tension developed by each contracting fibre (i.e., frequency of motor unit activation). Other factors influence the extent to which tension can be developed: MODULE 4 – MUSCLE PHYSIOLOGY - Frequency of stimulation - Length of the fibre at the onset of contraction - Extent of fatigue - Thickness of the fibre (number of myofibrils/sarcomeres) One action potential => twitch What happens with the repetition of the stimulation? Similar in principle to the temporal summation of EPSP at the postsynaptic neuron (but building tension in this case) 142  Twitch summation is possible because the duration of the action potential (1-2 msec) is shorter than the twitch duration (100 msec). Recall the refractory period: the fibre can be excited only once the absolute refractory period of the MODULE 4 – MUSCLE PHYSIOLOGY action potential is complete. The fibre can be re-stimulated while still in contraction. If repeated stimulations occur without allowing time for relaxation => Tetanus. 143  Take home points! MODULE 4 – MUSCLE PHYSIOLOGY Central nervous system can control muscle force through two key mechanisms 1) Motor unit recruitment (through Henneman’s size principle) 2) Motor unit activation rate (fusion of muscle twitches) BUT! What about the characteristics of the muscle? 143  Importance of initial muscle length on force development At optimal muscle length, maximum tension can MODULE 4 – MUSCLE PHYSIOLOGY be developed => Thin filaments optimally overlap regions of thick filament At greater than optimal length, tension production decreases linearly => Thin filaments are pulled out from between the thick filaments => Causes a decrease in available sites for crossbridge formation At less than optimal length, tension production decreases => Thin filaments overlap, limiting the number of active sites available for crossbridge formation 145  Isotonic and Isometric contractions Different types of muscle contractions… The force exerted by a muscle contraction on an object is known as muscle tension. MODULE 4 – MUSCLE PHYSIOLOGY The force exerted on a muscle by an object is known as muscle load. Muscle length changes will depend on the balance between tension and load. If tension > load = Shortening. If tension < load = lengthening When a muscle contracts without any shortening => Isometric contraction (= constant length). Contraction that involves constant load/tension = Isotonic contraction. This can be either an increase in muscle length (lengthening or eccentric contraction) or a decrease in muscle length (shortening or concentric contraction). iso = same tonic = tension metric = length 146  Consequence of the muscle load on muscle shortening Isometric contraction MODULE 4 – MUSCLE PHYSIOLOGY Ideal combination of force and velocity which produces maximal power (force x velocity) output Unloaded shortening velocity (Vmax) The greater the load, the lower the velocity of shortening Curve-linear relationship, known commonly as the force-velocity relationship Maximal force can be produced when velocity is zero (i.e., an isometric contraction) Maximal power is produced when optimal load and velocity relationship is determined 147  Skeletal muscle fibre types Three fibre types in human skeletal muscle Type I MODULE 4 – MUSCLE PHYSIOLOGY Type IIA Type IIX Different structural, functional, and metabolic characteristics across fibre types  Skeletal muscle fibre types MODULE 4 – MUSCLE PHYSIOLOGY 148  MODULE 4 – MUSCLE PHYSIOLOGY 151  MODULE 4 – MUSCLE PHYSIOLOGY 152