During normal function, acetylcholine (ACh) molecules re-leased to the synaptic cleft at the neuromuscular junction bind to the nicotinic ACh receptors on the sarcolemma of the skeletal muscle cell. As discussed earlier in the text, these re-ceptors represent transmitter-gated Nachannels that con-trol the influx of Nanecessary for generating an action potential leading to initiation of muscle contraction. After stimulating their own receptors, ACh molecules are quickly degraded by the enzyme acetylcholinesterase (AChE) into acetic acid and choline, which is taken up by the axon termi-nal and reused for ACh synthesis (see page 363). In a clinical condition called myasthenia gravis, the ACh nicotinic receptors are blocked by antibodies directed to the body’s own receptor protein. Thus, myasthenia gravis is an autoimmune disease caused by the reduced number of functional ACh receptor sites. In addition, other abnormalities within the synaptic cleft (e.g., widening of the synaptic cleft, disappearance of junctional folds) also occur, further reducing the effectiveness of the muscle fibers. Myasthenia gravis is characterized by noticeable weakening of the muscle fiber response to the nerve stim-ulus. Initially, weakness begins with extraocular muscles, drooping eyelids, double vision, and generalized muscular weakness. Other somatic musculature might be affected, including respiratory muscles. As the disease progresses, the number of neuromuscular junctions is reduced. An effective pharmacologic treatment for myasthenia gravis is administration of AChE inhibitors. These substances rein-force neuromuscular transmission by extending the life of released ACh within the synaptic cleft. In addition to AChE inhibitors, the immunosuppressive treatment and resection of the enlarged thymus (if present) are used to slow down the activity of the immune system and rate of production of antibodies against ACh receptors.
the somatic sensory system that provides information about the degree of stretching and tension in a muscle. Proprioreceptors inform the central nerve system about the body’s position and movement in space.
The muscle spindle is the specialized stretch receptor located within the skeletal muscle.
The muscle spindle is a specialized stretch receptor in muscle; it consists of two types of modified muscle fibers called spindle cells and neuron terminals (Fig. 11.12). Both types of modified muscle fibers are surrounded by an internal capsule. A fluid-filled space separates the internal capsule from an outer external capsule. One type of spindle cell, the nuclear bag fiber, contains an aggregation of nuclei in an expanded midregion; the other type, called a nuclear chain fiber, has many nuclei arranged in a chain. The muscle spindle transmits information about the degree of stretching in a muscle. The sensory (afferent, Ia) nerve fibers that carry information from the muscle spindle have endings that are spirally arranged around the midregion of both types of spindle cells. In addition, spindle cells receive motor (efferent) innervation from the spinal cord and brain via  motor (efferent) nerve fibers, which are thought to regulate the sensitivity of the stretch receptor. When skeletal muscle is stretched, nerve endings of sensory nerves become activated. They convey their impulses to the central nervous system, which in turn modulates the activity of motor neurons innervating that particular muscle.
Recent real-time studies with computed tomography (CT) scans of living muscle in different states of contraction suggest that muscle spindles may also represent the axes of functional units within large skeletal muscles. Such functional units precisely regulate contractions of portions of the muscle by creating “fixation points” within the muscle substance.