Fine structural localization of calcium binding sites in the neuromuscular junction.

By means of electron cytochemical analysis of rat neuromuscular junctions subjected to perfusion with a calcium-containing (5 mM) aldehyde fixative, two kinds of presynaptic calcium binding sites were demonstrated. "A" sites are located above openings of junctional folds; these triangular elements are identical with presynaptic protrusions of the active zone and probably comprise calcium channels of the presynaptic membrane, "B" sites, located within the terminal axoplasm, are associated to multivesicular bodies probably accumulating surplus intracellular calcium. This fine structural arrangement enables a highly parsimonious usage of extracellular calcium in inducing release of acetylcholine from synaptic vesicles. Junctional folds of the postsynaptic membrane may funnel calcium ions exactly to spatially restricted calcium channels. Having entered the terminal through the channels opened by the arrival of nerve action potential, calcium ions may exert their action upon synaptic vesicles accumulated in the closest vicinity by means of stripping off hydration barriers and by inducing membrane fusions, that finally result in quantal release of acetylcholine from the terminal.