title: Presynaptic calcium influx, neurotransmitter release, and neuromuscular disease.
abstract: The synapse between a spinal motor neuron and a muscle cell is normally very effective at eliciting muscle contraction. A reliable connection between these two cells occurs because a single action potential reaching the motor nerve terminal normally releases hundreds of packets of transmitter containing thousands of chemical transmitter molecules, which cross the synapse and encounter a specialized region of postsynaptic muscle. Within the muscle membrane are thousands of receptor proteins specific for this transmitter. Activation of these postsynaptic receptors allows positively charged ions to cross the muscle membrane, generating a muscle cell action potential that leads to muscle contraction. Because of its size, contraction of a muscle cell requires the activation of an exceptionally large number of neurotransmitter receptors. To understand the regulation of this reliable communication and to elucidate details of pathological conditions that lead to muscle weakness, we have studied the subcellular mechanisms that govern synaptic transmission at the neuromuscular junction (NMJ). This article will review recent electron microscopic, electrophysiological, and imaging data in a discussion of the function of the motor nerve terminal in both normal and diseased states. Taken together, the existing data lead us to hypothesize that a small fraction of available calcium channels open within the transmitter releasing regions of the NMJ and that each vesicle fusion event is triggered by calcium flux through a single channel opening.
authors.affiliation: Department of Neuroscience, University of Pittsburgh, 446 Crawford Hall, 15260, Pittsburgh, PA, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Poage
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Meriney
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D006801:Humans; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism; D009422:Nervous System Diseases / Q000473:pathology; D009468:Neuromuscular Diseases / Q000378:metabolism* / Q000473:pathology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D017661:Receptors, Presynaptic / Q000187:drug effects*
chemical_list: D018377:Neurotransmitter Agents; D017661:Receptors, Presynaptic; D002118:Calcium