Neurotransmitter release at rapid synapses

The classical concept of the vesicular hypothesis for acetylcholine (ACh) r elease, one quantum resulting from exocytosis of one vesicle, is becoming m ore complicated than initially thought. 1) synaptic vesicles do contain ACh , but the cytoplasmic pool of ACh is the first to be used and renewed on st imulation. 2) The vesicles store not only ACh, but also ATP and Ca2+ and th ey are critically involved in determining the local Ca2+ microdomains which trigger and control release. 3) The number of exocytosis pits does increas e in the membrane upon nerve stimulation, but in most cases exocytosis happ ens after the precise time of release, while it is a change affecting intra membrane particles which reflects more faithfully the release kinetics. 4) The SNARE proteins, which dock vesicles close to Ca2+ channels, are essenti al for the excitation-release coupling, but quantal release persists when t he SNAREs are inactivated or absent. 5) The quantum size is identical at th e neuromuscular and nerve-electroplaque junctions, but the volume of a syna ptic vesicle is eight times larger in electric organ; at this synapse there is enough ACh in a single vesicle to generate 15-25 large quanta, or 150-2 00 subquanta. These contradictions may be only apparent and can be resolved if one takes into account that an integral plasmalemmal protein can suppor t the formation of ACh quanta. Such a protein has been isolated, characteri sed and called mediatophore. Mediatophore: has been localised at the active zones of presynaptic nerve terminals. It is able to release ACh with the e xpected Ca2+-dependency and quantal character, as demonstrated using mediat ophore-transfected cells and other reconstituted systems. Mediatophore is b elieved to work like a pore protein, the regulation of which is in turn lik ely to depend on the SNARE-vesicle docking apparatus, (C) 2000 societe fran caise de biochimie et biologie moleculaire / Editions scientifiques et medi cales Elsevier SAS.