Protein kinase C is an enzyme whose activity depends on its lipid environment and which is activated by the second messenger, diacylglycerol. The high concentrations of protein kinase C in the nervous system compared to many other tissues suggest that this enzyme plays an important role in the regulation of neuronal activity. Its physiological activator, diacylglycerol, is produced transiently in many types of cells in response to synaptic or hormonal stimulation. In intact cells, the activity of protein kinase C can be stimulated by low concentrations of phorbol esters or by synthetic diacylglycerols. Both biochemical and electrophysiological investigations using activators of this enzyme have indicated that protein kinase C regulates calcium, potassium and chloride channels, and that changes in its activity control the amount of neurotransmitter released by nerve cells.

Prolonged changes in excitability can follow brief stimulation of a neurone. These include changes in endogenous firing pattern, which may be used to trigger and control prolonged animal behaviors, and long-lasting changes in synaptic efficacy, such as are observed in the phenomenon of long-term potentiation in the hippocampus. Such transformations in firing pattern or transmitter release may be induced in response to synaptic stimulation by the activation of a second messenger system. The best studied second messenger system to date is the adenylate cyclase/cyclic AMP-dependent protein kinase system. It has recently become clear that another second messenger system, linked to the activation of a calcium/diacylglycerol/phospholipid-dependent protein kinase, also termed protein kinase C, plays a central role in the regulation of neuronal excitability.