Protein kinase C: A physiological mediator of enhanced transmitter output

Protein kinase C (PKC), activated by either diacylglycerol and/or arachidonic acid, through the activation of presynaptic receptors or nerve depolarization is involved in the enhancement of transmitter release from many neural types. This facilitation is most likely mediated by the phosphorylation of proteins involved in vesicle dynamics although a role for ion channels cannot be ruled our. PKC is not fundamental to the release process but rather has a modulatory role. In some systems the role of PKC is to help maintain transmitter output during prolonged or elevated levels of activation and this seems to parallel suggestions that PKC is involved in the movement of reserve pools of vesicles into release-ready sites. Presynaptic facilitatory actions mediated by PKC are also involved in integrated modulatory functions such as long term potentiation, again where it elevates or maintains transmitter output. Although studies have tried to identify specific roles for the various PKC isoforms, the actions of phorbol esters in elevating transmitter release do not fit with known potencies on individual isoforms and it is suggested that PKC may be located at an intraneuronal location which is difficult to access for lipophilic phorbol esters and further work is required ill this area. (C) 1998 Elsevier Science Ltd. All rights reserved.