<P> Neuromuscular junction diseases can be of genetic and autoimmune origin . Genetic disorders, such as Duchenne muscular dystrophy, can arise from mutated structural proteins that comprise the neuromuscular junction, whereas autoimmune diseases, such as myasthenia gravis, occur when antibodies are produced against nicotinic acetylcholine receptors on the sarcolemma . </P> <P> At the neuromuscular junction presynaptic motor axons terminate 30 nanometers from the cell membrane or sarcolemma of a muscle fiber . The sarcolemma at the junction has invaginations called postjunctional folds, which increase its surface area facing the synaptic cleft . These postjunctional folds form the motor endplate, which is studded with nicotinic acetylcholine receptors (nAChRs) at a density of 10,000 receptors / micrometer . The presynaptic axons terminate in bulges called terminal boutons (or presynaptic terminals) that project toward the postjunctional folds of the sarcolemma . In the frog each motor nerve terminal contains about 300,000 vesicles, with an average diameter of 0.05 micrometers . The vesicles contain acetylcholine . Some of these vesicles are gathered into groups of fifty, positioned at active zones close to the nerve membrane . Active zones are about 1 micrometer apart . The 30 nanometer cleft between nerve ending and endplate contains a meshwork of acetylcholinesterase (AChE) at a density of 2,600 enzyme molecules / micrometer, held in place by the structural proteins dystrophin and rapsyn . Also present is the receptor tyrosine kinase protein MuSK, a signaling protein involved in the development of the neuromuscular junction, which is also held in place by rapsyn . </P> <P> About once every second in a resting junction randomly one of the synaptic vesicles fuses with the presynaptic neuron's cell membrane in a process mediated by SNARE proteins . Fusion results in the emptying of the vesicle's contents of 7000 - 10,000 acetylcholine molecules into the synaptic cleft, a process known as exocytosis . Consequently exocytosis releases acetylcholine in packets that are called quanta . The acetylcholine quantum diffuses through the acetylcholinesterase meshwork, where the high local transmitter concentration occupies all of the binding sites on the enzyme in its path . The acetylcholine that reaches the endplate activates ~ 2,000 acetylcholine receptors, opening their ion channels which permits sodium ions to move into the endplate producing a depolarization of ~ 0.5 mV known as a miniature endplate potential (MEPP). By the time the acetylcholine is released from the receptors the acetylcholinesterase has destroyed its bound ACh, which takes about ~ 0.16 ms, and hence is available to destroy the ACh released from the receptors . </P> <P> When the motor nerve is stimulated there is a delay of only 0.5 to 0.8 msec between the arrival of the nerve impulse in the motor nerve terminals and the first response of the endplate The arrival of the motor nerve action potential at the presynaptic neuron terminal opens voltage - dependent calcium channels and Ca ions flow from the extracellular fluid into the presynaptic neuron's cytosol . This influx of Ca causes several hundred neurotransmitter - containing vesicles to dock and fuse to the presynaptic neuron's cell membrane through SNARE proteins to release their acetylcholine quanta by exocytosis . The endplate depolarization by the released acetylcholine is called an endplate potential (EPP). The endplate potential sets up an action potential in the muscle fiber which triggers contraction . The transmission from nerve to muscle is so rapid because each quantum of acetylcholine reaches the endplate in millimolar concentrations, high enough to combine with a receptor with a low affinity, which then swiftly releases the bound transmitter . </P>

Region on muscle fiber that contains ach receptors