The neuromuscular junction

The neuromuscular junction is a synapse between the tightly apposed presynaptic motor neuron terminal and the postsynaptic muscle fiber; this is where a chemical process (release of acetylcholine [ACh] from the nerve ending) leads to an electrical event (muscle membrane depolarization) resulting in a mechanical effect (muscle contraction) (Figure 44-1). Large motor nerve axons branch as they course distally within skeletal muscle. Ultimately, the axons divide into 10 to 100 smaller terminal nerve fibers, lose their myelin sheath, and innervate a single muscle fiber. The combination of the terminal neural fibers that originate from 1 axon and the muscle fibers they innervate form a motor unit. The average number of muscle fibers innervated by a single motor neuron defines the innervation ratio, which, in humans, varies between 1:5 and 1:2000. For smaller muscles that are specialized in fine and precise movement (such as the hand and ocular muscles), the innervation ratio is low (1:5, or 5 muscle fibers per neuron), whereas large antigravity muscles have very high innervation ratios (1:2000). Transmission from nerve to muscle is mediated by ACh, which is synthesized in the nerve terminal and stored in specialized vesicles. Each nerve terminal contains approximately 500,000 vesicles (also called quanta, and each containing 6-10,000 ACh molecules) arranged in a specialized region of the membrane where the synaptic vesicles gather, the active zone. ACh is released by exocytosis into the junctional cleft after an appropriate nerve impulse reaches the nerve terminal and diffuses across the 50- to 70-nm cleft to bind the nicotinic cholinoceptors on the postjunctional muscle membrane and initiate muscle contraction.

ACh is synthesized from acetyl coenzyme A and choline under the catalytic influence of choline O-acetyltransferase (CAT) enzyme in the axoplasm (Figure 44-2). The ACh is transported into vesicles by a specific carrier-mediated system. Approximately 80% of the ACh present in the nerve terminal is located in the vesicles, with the remainder dissolved in the axoplasm.