Autoreceptors, membrane potential and the regulation of transmitter release

It has been suggested that depolarization per se can control neurotransmitt er release, in addition to its role in promoting Ca2+ influx. The Ca2+ hypo thesis' has provided an essential framework for understanding how Ca2+ entr y and accumulation in nerve terminals controls transmitter release. Yet, in creases in intracellular Ca2+ levels alone cannot: account for the initiati on and termination of release; some additional mechanism is needed. Several experiments from various laboratories indicate that membrane potential has a decisive role in controlling this release. For example, depolarization c auses release when Ca2+ entry is blocked and intracellular Ca2+ levels are held at an elevated level. The key molecules that link membrane potential w ith release control have not yet been identified:likely candidates are pres ynaptic autoreceptors and perhaps the Ca2+ channel itself.