Reliability of neuromuscular transmission and how it is maintained.

An important function of all nervous systems is to control muscle contraction so that movements of the body are appropriate to promote survival. In most species specialized motor neurons convey the signals that represent the neural commands for contraction from the central nervous system to the muscle fibers. These signals are transmitted to the individual muscle fibers at highly differentiated neuromuscular junctions (NMJs). The process of neuromuscular transmission involves the rapid release of multimolecular " quanta " of acetylcholine (ACh) from the nerve, the binding of the ACh to ligand-gated cation channels (ACh receptors, AChRs) in the surface of the muscle fiber, the opening of those channels and the flow of current into the muscle fiber leading to depolarization and opening of voltage-gated sodium channels causing initiation of an action potential (AP) and contraction of the muscle cell. In most vertebrates, each motor neuron provides the sole innervation for each of many muscle fibers. A fundamental design principle of neuromuscular systems in higher vertebrates, including humans, is that every nerve impulse in a motor neuron should evoke contraction of every muscle fiber innervated it. Au2 Thus each motor neuron, and the muscle fibers it innervates, operates as a " motor unit ". For this principle to be realized in practise, it is essential that the process of neu-romuscular transmission should be reliable, operating unfailingly over a wide range of functional demands. The reliability of transmission at the NMJ sets it apart from most other chemical synapses. In the central nervous system (CNS) the impact of individual synapses on the postsynaptic cell must generally be small, to allow many inputs to influence the final output. At the NMJ just the opposite is true. To ensure that each nerve impulse triggers muscle contraction, its impact on the muscle fiber is usually significantly greater than required to trigger an AP. For this reason, the process of neuromuscular transmission is said to have a big " safety factor ". This results from specializa-tions of both pre-and postsynaptic components. While the immediate molecular processes of neuromuscular transmission are qualitatively similar to those at central synapses, the distinctive functional organization of the NMJ is what accounts for its essential reliability. To understand the basis of the reliability of neuro-muscular transmission, it is therefore just as important to know how NMJs differ from central synapses as how they resemble them. This understanding provides the necessary foundation for …