Activation of protein kinase C augments evoked transmitter release

In view of the emerging role of the phosphoinositide system in cellular communication^1,2 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 membrane^4,5 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 secretion^8-13 and enhance calcium currents^14,15; 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.