Muscle formation: EC coupling & mechanisms of contraction

===Lecture Details===
Wayne Sturrock; Week 4 MED1022; Physiology
===Lecture Content===
Plasma membrane (sarcolemma) surrounds the cell, is an exciteable membrane (propagates action potential). Transverse tubules (T tubules) are radial invaginations of the sarcolemma, open to the extracellular space and are an exciteable membrane. Action potentials propagate into T tubules.
Sarcoplasmic reticulum is an intracellular compartment and has a sleeve-like structure surrounding each myofibril. It comes in close association with T tubule membrane but no contact. Is responsible for Ca uptake and storage along with Ca release. A Ca pump in the SR pumps Ca into it from the cytoplasm, pumps against a concentration gradient (107 to 103) so needs energy; uses ATP. Release by the SR is initiated by T tubule depolarisation (when an AP propagates to the muscle), causes Ca release channels to open, flows into the cytoplasm down the concentration gradient. There are voltage sensors in the T tubule membrane (dihydropyridine receptors) which communicate in some way with the ryanodine receptors in the SR release channels. Lateral sacs of the SR come in close contact with the T tubules. Ryanodine receptors face toward the T tubule membrane. Voltage receptors (dihydropyridine) face the ryanodine receptors.
Excitation contraction coupling goes from AP > T tubules > SR > Ca release > Ca binding to troponin > Movement of tropomyosin to uncover myosin binding sites on actin > Myosin binds to actin > Crossbridge cycling > Contraciton. When AP has gone, Ca release channels in SR close and Ca release stops. SR pumps Ca back in, removing it from troponin. Tropomyosin blocks myosin binding sites on actin.
Central core diseas is mutation in ryanodine leading to impairment in Ca release. Symptoms include hypotonia and persistent muscle weakness, generally seen in infants. Malignant hyperthermia is due to ryanodine mutation which sensitises the Ca release mechanism, leading to uncontrolled Ca release. There is excessive skeletal muscle metabolic activity. It is triggered by exposure to drugs used for anaesthesia, and reaction overwhelms oxygen supply and CO2 removal as well as temperature regulation leading to circulatory collapse and death.
Isometric contraction is where muscle stays a fixed length, generates force but does not shorten. Isotonic contraction is where a muscle contracts against a constant load (shortens and moves the load). Eccentric contraction is where it stretches while contracting eg stretching quadriceps walking down a hill, can lead to DOMS. Mechanical nature of contraction determined by motor command and external restraints on muscle.
There are agonist and antagonist muscles. To hold a weight in the hand there must be bicep force 7 times that of the weight, speed is amplified 7 times in terms of movement of the hand. Lever advantage of joints allows for building up of force in throwing. Passive force is when a resting muscle is stretched, is unrelated to contraction, demonstrates elastic capacity, mainly due to connective tissue. Active is generated by crossbridges, depends on the length of the muscle.
At optimal length all crossbridges can generate force. Is the length of maximum force. At longer lengths less crossbridges can attach. At shorter lengths force decreases as there is double overlap of filaments, Z lines are hit causing muscle to buckle and also less Ca is released for unknown reasons. Range of length changes is limited by attachment to bones. Most muscles are at optimal length in resting position and have operating range of about 30% from this (Lo).
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