The force of muscle contraction can be modulated by various factors. In skeletal muscle, the transmission of an action potential occurs at the neuromuscular junction between an α motor neuron and the muscle fiber. Acetylcholine released by the motor neuron initiates an action potential in the muscle fiber, which quickly spreads along its length. The duration of the action potential in skeletal muscle is less than 5 msec. This action potential triggers the release of calcium ions from the terminal cisternae of the sarcoplasmic reticulum (SR). These calcium ions promote the interaction between actin and myosin, leading to muscle contraction.

A thick filament is formed by the polymerization of myosin molecules in a tail-to-tail configuration. Each myosin molecule consists of a tail region and a cross-bridge region. The cross-bridge region contains globular heads with light chains, which are important for the function of myosin ATPase activity.

When the action potential is transmitted along the sarcolemma and T tubules, calcium ions are released from the terminal cisternae of the SR into the myoplasm. This increase in intracellular calcium concentration initiates a contraction known as a twitch. The elevation in intracellular calcium concentration begins shortly after the action potential and reaches its peak at around 20 msec.

The mechanism underlying the increase in intracellular calcium involves an interaction between proteins in the T tubule and the adjacent terminal cisternae of the SR. The T tubule, which represents an invagination of the sarcolemma, forms a close association with two terminal cisternae of the SR, creating a triad. Bridging proteins called feet span the gap between the T tubule and the terminal cisternae. These feet, also known as ryanodine receptors, are responsible for the release of calcium ions in response to the action potential. The ryanodine receptor is a large protein that exists as a homotetramer, with only a small portion embedded in the SR membrane. Most of the ryanodine receptor spans the gap between the terminal cisternae and the T tubule.
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