[Release of acetylcholine and its regulation]

The mechanism of acetylcholine (ACh) release and its regulation is a widely studied subject still underdebated. Although the vesicular hypothesis for ACh release is at present largely accepted, alternative theories have been proposed. ACh release is triggered by calcium influx through specific presynaptic Ca2+ channels. The modulation of this calcium influx appears as the main mechanism through which ACh release is regulated. This can be achieved by direct modification of the presynaptic Ca2+ channel opening or indirectly by a change in the polarization level of the presynaptic membrane due to the opening or closing of other presynaptic channels (usually K+ channels). The increase in the intracellular Ca2+ concentration that triggers ACh release is also under the control of Ca2+ membrane exchanges and intracellular Ca2+ buffers. ACh synthesis that takes place in the cytoplasm of the terminal, can itself be modulated leading to changes in the quantity of ACh available for release. All these regulatory mechanisms can be initiated by the activation of presynaptic receptors to either ACh itself (autoreceptors) or to other transmitters (heteroreceptors). Most often, these presynaptic receptors seem to require the transducing role of G proteins and the involvement of various second messengers. Some illnesses concerning the cholinergic system can be related to a disfunction of one of these presynaptic regulatory mechanisms.