NANC transmission at a varicosity: the individuality of single synapses

Abstract

Nerve terminals consist of several hundred varicosities or synapses, each with a single active zone. The smooth muscle membrane apposing varicosities within about 50 nm is occupied by a 1-μm diameter cluster of P2X₁ receptors together with a mixture of other P2X subtypes; the rest of the membrane possesses small (0.4 μm diameter) clusters of P2X₁ to P2X₆ subunits. The small P2X clusters appear to form large clusters during development. This is supported by the observation that chimeras of P2X₁ subunits and green fluorescent protein (P2X₁-GFP), when packaged into adenoviruses used to infect excitable cells, initially form a diffuse distribution of small clusters of P2X₁-GFP in the membrane; these can be later observed in real time to form large clusters. Recording the electrical signs of ATP release from single adjacent varicosities, or using antibodies to label the extent of exocytosis from them, shows that they release with quite different probabilities. There are large quantitative differences in the extent of P2X autoreceptors on the membranes of individual varicosities. These will contribute to the differences in the probability of secretion from individual varicosities. The present analysis of NANC transmission at single varicosities indicates that individual synapses possess different probabilities for the secretion of transmitter as well as different complements of autoreceptors and mixtures of postjunctional receptor subunits.