Skeletal Muscle Neuromuscular junction with ACh and nicotinic receptors. Start o

Question

Skeletal Muscle Neuromuscular junction with ACh and nicotinic receptors. Start of action potential, why skeletal muscle is all or none. Excitation-contraction coupling between T-tubles and sarcoplasmic reticulum to release Ca+2 for allosteric regulation of contraction cycle, troponin, tropomyosin actin and myosin cross-bridge cycling and where and how ATP is used. Define motor unit. Know about Spatial summation (recruitment) and temporal summation (tetany)/ fatigue/ isometric vs. isotonic contractions. Understand how the length- tension relationship works for passive lengthening and shortening of the muscle. What is the metabolism of skeletal muscle cells, how does this effect speed of movement, size of cells and recruitment order? What about fatigue?

Explanation / Answer

Ans. The law of all-or-none states that response to a particular stimulus by a nerve or myscle fiber is independent  of the strength of the stimulus. Upon exceeding the threshold potential of the stimulus, the nerve or muscle fiber gives a complete response or no response at all.Thus, it is stated that the degree of action potential initiated in any single nerve fiber is independent of the strength of the exciting stimulus, provided the strength of the stimuli is adequate. An electrical stimulus below threshold strength fails to elicit the desired potential.This property of the single nerve fiber is termed the all or none relationship. This relationship holds true for the unit of tissue; the nerve cell, individual muscle fiber for the skeletal muscle involved and the entire auricles/the ventricles for the heart muscle.

#Where and how ATP is used:

The calcium ions regulates the linking of muscle excitation to calcium release from the sarcoplasmic reticulum by a phenomenon called excitation-contraction coupling.The T-tubules (tube-shaped invaginations of the sarcolemma that runs across the skeletal muscle fiber.)are indispensible for the coupling process.The action potential is transmitted into the muscle fiber interiors by T-tubules. On either side of the T-tubule , there is the presence of swelled ,regularly spaced structures called lateral sacs which were physiologically termed as feet . Subsequent molecular studies have identified the feet as being part of the calcium channel protein in the membrane of the sarcoplasmic reticulum.The T-tubule voltage sensor is located in close proximity to the calcium channel in the T-tubule membrane,. The voltage sensor changes conformation in response to the depolarization of the action potential. This conformational change is transmitted to the foot of the sarcoplasmic reticulum calcium channel, allowing it to open with subsequent release of calcium ions.

Skeletal muscle contractions are triggered by action potentials generated in the outer cell membrane. Under normal conditions, an action potential deploarize from a resting membrane potential of ?80 mV to +30 mV, followed by repolarization, where the membrane potential returns to its resting value. The depolarization depends on Na+ influx through voltage-gated Na+ channels, and the repolarization involves K+ efflux through voltage-gatedK+channels (Kv). Each action potential propagates along the surface membrane and into the transverse tubules. Depolarization of the transverse tubules is detected by voltage-sensitive Ca++ channels known as dihydropyridine receptors.These receptors communicate with Ca2+ channels(ryanodine receptors) to release Ca++ from the sarcoplasmic reticulum. At low Ca++ concentrations, tropomyosin blocks the myosin-binding site on actin. When Ca2++ concentration increases in response to an action potential, it binds to troponin and a seven monomers long actin segment. Thus, it becomes available to myosin as one tropomyosin is moved away from the myosin-binding site on actin.

ATP provides the energy in the muscles by utilising myosin ATPases, terminating contraction by pumping Ca2+ back into the sarcoplasmic reticulum, achieved by Ca2+ ATPase. The preserved ATP content is manintained by control of metabolic pathways providing ATP and the regulation of the processes that use ATP.The use of ATP can be mimimised by decreasing Ca2+ release within each cell upon muscle contration which utilises myosin ATPase. A lower level of Ca2+ release can be accomplished by control of membrane potential and by direct regulation of the ryanodine receptor .Three major proteins contribute to increased ATP use during contraction.They are ,(i) Na+/K+-ATPase,(ii) myosin ATPase and (iii)Ca2+ ATPase.

The Na+/K+-ATPase pumps Na+ back out and K+ back into the fiber after an action potential.

The myosin ATPase uses ATP to generate force and do work.

The Ca2+ ATPase is responsible for pumping Ca2+ back into the sarcoplasmic reticulum allowing muscle relaxation.

Each of these ATPases, contributes respectively about (10,60,30)% of total ATP use.

#Motor unit:

A motor unit consists of a somatic efferent motor neuron and the skeletal muscle fibers innervated by the motor neuron's axonal terminals.Motor unit groups perform together ,coordinating the contractions of a single muscle. The group of motor units within a muscle is a motor pool. All muscle fibres in a motor unit are of the same fibre type. Upon activation of a motor unit, all of its fibres contract.The force of a muscle contraction is controlled by the number of activated motor units.This concept of motor unit was first put down by Charles Scott Sherrington.

#Metabolism of skeletal muscle cells:A skeletal muscle upon contration uses a number of intramuscular and extramuscular substrates to generate ATP. These include creatine phosphate, muscle glycogen, blood glucose, lactate and free fatty acids (FFA), derived from adipose tissue / intramuscular triglyceride storehouse.During high-intensity short-duration exercise, creatine phosphate degradation vis-a-vis breakdown of muscle glycogen to lactate are the prominent energy yielding pathways apart from the contribution of oxidative metabolism. The anaerobic substrates serve as fuels during the transition from rest to steady state exercise.The oxidative metabolism of carbohydrate and lipid supplies the ATP during prolonged submaximal exercise. Muscle glycogen, blood glucose and FFA are the key fuels. The relative importance of the various substrates for skeletal muscle metabolism is determined by exercise intensity and duration.

#Fatigue:Muscular fatigue is the inability of a muscle to generate the desired force.This stems from streinous exercise.There are two underlying reasons for muscle fatigue.They are:

(i) the inability of a nerve to generate a prolonged signal termed as neural fatigue.

(ii) the reduced ability of a muscle fiber to contract called metabolic fatigue.

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