[Molecular mechanisms of mediator secretion]

A review is presented discussing problems of transmitter localization in nerve endings, their replenishment in synaptic vesicles (SV), reuptake of transmitters and their degradation products from the synaptic cleft, the structural variations in the presynaptic membrane (pre-SM) during rest and excitation and the role of contractile proteins in the mechanism underlying transmitter secretion. A hypothesis is proposed about the universality of the mechanisms involved in transmitter release and utilization and the key role of the membrane ATP-ase system in these processes. During depolarization of the pre-SM the increase in membrane permeability is ascribed to the loosening of protein-lipid bonds and inhibition of ATP-ase activity involved in transport mechanisms. During depolarization the number of complementary contacts between SV and the pre-SM increase probably through the action of myosin-like and actin-like proteins localized on the SV and pre-SM, respectively. The release of transmitters and polypeptides is thought to be initiated by an increased concentration of Ca2+ in the synaptoplasm which induces contraction of the actomyosin-like complex. Changes in the Na-gradient brought about by the activity of Na, K-ATP-ase, are involved in the active reuptake of transmitters from the synaptic cleft. The newly-synthesized transmitters and those taken up from the synaptic cleft are stored in the SV by a Mg-ATP-ase dependent mechanism. Transmitters are stored in SV bound to acid polypeptides containing nucleotides. The presynaptic action of different neurotoxins is also discussed.