Skeletal muscle fibers contract only under the control of the nervous system. Communication between the nervous system and a skeletal muscle fiber occurs at a specialized intercellular connection known as a neuromuscular junction (NMJ), or myoneural junction. One such junction is shown in Figure 10-9a.

The Neuromuscular Junction

Each skeletal muscle fiber is controlled by a neuron at a single neuromuscular junction midway along the fiber's length. Figure 10-9b summarizes key features of this structure. A single axon branches within the perimysium to form a number of fine branches. Each branch ends at an expanded synaptic terminal. The cytoplasm of the synaptic terminal contains mitochondria and vesicles filled with molecules of acetylcholine, or ACh. Acetylcholine is a neurotransmitter, a chemical released by a neuron to change the membrane properties of another cell. In this case, the release of ACh from the synaptic terminal can alter the permeability of the sarcolemma and trigger the contraction of the muscle fiber.

The synaptic cleft, a narrow space, separates the synaptic terminal of the neuron from the opposing sarcolemmal surface. This surface, which contains membrane receptors that bind ACh, is known as the motor end plate. The motor end plate has deep creases called junctional folds, which increase its surface area and thus the number of available ACh receptors. The synaptic cleft and sarcolemma also contain molecules of the enzyme acetylcholinesterase (AChE, or cholinesterase), which breaks down ACh.

When a neuron stimulates a muscle fiber, the stimulus for ACh release is the arrival of an electrical impulse, or action potential, at the synaptic terminal. An action potential is a sudden change in the transmembrane potential propagated along the length of the axon. When that impulse reaches the synaptic terminal, permeability changes in the membrane trigger the exocytosis of ACh into the synaptic cleft. This exocytosis is accomplished when vesicles in the synaptic terminal fuse with the membrane of the neuron.

Molecules of ACh diffuse across the synaptic cleft and bind to ACh receptors on the motor end plate. The binding of ACh changes the permeability of the motor end plate to sodium ions (Figure 10-9c). As we learned in Chapter 3, the extracellular fluid contains a high concentration of sodium ions, whereas sodium ion concentrations inside the cell are very low.    When the membrane permeability to sodium increases, sodium ions rush into the sarcoplasm. This influx continues until AChE removes the ACh from the receptors.

The sudden influx of sodium ions results in the generation of an action potential in the sarcolemma at the edges of the motor end plate. This electrical impulse sweeps across the entire membrane surface and travels along each T tubule. The arrival of an action potential at the synaptic terminal thus leads to the appearance of an action potential in the sarcolemma. Even before the action potential has spread across the entire membrane, the ACh has been broken down by AChE. This sequence of events can now be repeated if another action potential arrives at the synaptic terminal.

Excitation–Contraction Coupling

The link between the generation of an action potential in the sarcolemma and the start of a muscle contraction is called excitation–contraction coupling. This coupling occurs at the triads. On reaching a triad, an action potential triggers the release of Ca²⁺ from the cisternae of the sarcoplasmic reticulum. The change in the permeability of the SR to Ca²⁺ is temporary, lasting only about 0.03 second. Yet within a millisecond the Ca²⁺ concentration in and around the sarcomere reaches 100 times resting levels. Because the terminal cisternae are situated at the zones of overlap, where the thick and thin filaments interact, the effect of calcium release on the sarcomere is almost instantaneous. The binding of Ca²⁺ to troponin exposes the active sites along the thin filaments, initiating the contraction. The contraction cycle then begins.

During the contraction cycle, cross-bridges bind to exposed active sites and the myosin heads pivot, shortening the sarcomeres. Each myosin head continues to attach, pivot, and detach as long as Ca²⁺ and ATP are available. This process is detailed in Figure 10-10 , in "FOCUS: The Contraction Cycle".

Anything that interferes with neural function or with excitation–contraction coupling will cause muscular paralysis. Two examples are worth noting:

1. Botulism results from the consumption of contaminated canned or smoked foods that contain a toxin. The toxin, produced by bacteria, prevents the release of ACh at the synaptic terminals, leading to a potentially fatal muscular paralysis.

2. The progressive muscular paralysis of myasthenia gravis results from the loss of ACh receptors at the junctional folds. The primary cause is a misguided attack on the ACh receptors by the immune system. Genetic factors play a role in predisposing individuals to this condition. Problems with the Control of Muscle Activity