AN ION CHANNEL LOCUS FOR THE PROTEIN-KINASE-C POTENTIATION OF TRANSMITTER GLUTAMATE RELEASE FROM GUINEA-PIG CEREBROCORTICAL SYNAPTOSOMES

The mechanisms by which protein kinase C (PKC) activates transmitter release from guinea pig cerebrocortical synaptosomes was investigated by employing parallel fluorescent assays of glutamate release, cytoplasmic free Ca2+, and plasma membrane potential. 4-beta-Phorbol dibutyrate (4-beta-PDBu) enhances the Ca2+-dependent, 4-aminopyridine (4AP)-evoked release of glutamate from synaptosomes, the 4AP-evoked elevation of cytoplasmic free Ca2+, and the 4AP-evoked depolarization of the plasma membrane. 4-beta-PDBu itself causes a slow depolarization, which may underlie the small effect of 4-beta-PDBu on spontaneous, KCl-evoked, and Ca2+-independent/4AP-evoked glutamate release. Because 4AP (but not KCl) generates spontaneous, tetrodotoxin-sensitive action potentials in synaptosomes, a major locus of presynaptic PKC action is to enhance these action potentials, perhaps by inhibiting delayed rectifier K+ channels.