Modulation of the Force of Contraction ”). neuron is called an end plate (see for details). Acetylcholine released from the α motor neuron at the neuromuscular junction initiates an action potential in the muscle fiber that rapidly spreads along its length. When an action potential is transmitted along the sarco-The duration of the action potential in skeletal muscle is lemma of the muscle fiber and then down the T tubules, less than 5 msec. The duration of the action potential in Ca++ is released from the terminal cisternae SR into the
Globular heads (S-1) with light chains Proteolytic cleavage • Fig. 12.6. Organization of a Thick Filament. A thick filament is formed by the polymerization of myosin molecules in a tail-to-tail configuration extending from the center of the sarcomere (A). An individual myosin molecule has a tail region and a cross-bridge region. The cross-bridge region is composed of an arm and globular heads (B). The globular heads contain light chains that are important for the function of myosin ATPase activity. LMM, light meromyosin; S-1 and S-2, myosin subfragments 1 and 2.
myoplasm. This release causes intracellular [Ca++] to rise, which in turn promotes actin-myosin interaction and contraction. The time course for the increase in intracellular [Ca++] in relation to the action potential and development of force is shown in
Fig. 12.8 . The action potential is extremely short-lived (≈5 msec). The elevation in intracellular [Ca++] begins slightly after the action potential and peaks at approximately 20 msec. This increase in intracellular [Ca++] initiates a contraction called a twitch.
The mechanism underlying the elevation in intracellular [Ca++] involves an interaction between protein in the T tubule and the adjacent terminal cisternae of the SR. As previously described (see
Fig. 12.3 ), the T tubule represents an invagination of the sarcolemma that extends into the muscle fiber and forms a close association with two terminal cisternae of the SR. The association of a T tubule with two opposing terminal cisternae is called a triad. Although there is a gap (≈15 nm in width) between the T tubule and the terminal cisternae, proteins bridge this gap. On the basis of their appearance on electron micrographs, these bridging proteins are called feet (
Fig. 12.9 ). These feet are the Ca++ release channels in the membrane of the terminal cisternae that are responsible for the elevation in intracellular [Ca++] in response to the action potential. Because this channel binds the drug ryanodine, it is commonly called the ryanodine receptor (RYR). RYR is a large protein (≈500 kDa) that exists as a homotetramer. Only a small portion of the RYR molecule is actually embedded in the SR membrane.
Most of the RYR molecule appears to be in the myoplasm and spans the gap between the terminal cisternae and the T tubule (
Fig. 12.10