Activation of protein kinase C augments evoked transmitter release

Abstract

In view of the emerging role of the phosphoinositide system in cellular communication1,2 we examined its involvement in quantal transmitter release, which is a key element in synaptic transmission3. Transmitter release is normally activated by an increase in intracellular calcium, achieved either by entry of calcium ions through the presynaptic membrane4,5 or by intracellular calcium liberation6. One of the targets of the phosphoinositide signalling system is the enzyme protein kinase C (PKC), which can be activated experimentally by tumour promoting phorbol esters, including 12-O-tetradecanoyl phorboI-13-acetate (TPA)7. Such activation of PKC may be implicated in transmitter release in two ways. First, phorbol esters were found to increase secretion8–13 and enhance calcium currents14,15; it might therefore be expected that they would increase synaptic transmitter release. But phorbol esters also inhibit the calcium current in dorsal root ganglion neurones16. We report that the phorbol ester TPA augments synaptic transmission at the neuromuscular junction by increasing transmitter liberation. Activation of PKC also deepens synaptic depression.