An Ion Channel Locus for the Protein Kinase C Potentiation of Transmitter Glutamate Release from Guinea Pig Cerebrocortical Synaptosomes

Abstract
The mechanism 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. 4β-Phorbol dibutyrate (4β- 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. 4β-PDBu itself causes a slow depolarization, which may underlie the small effect of 4β-PDBu on spontaneous, KCI-evoked, and Ca2+-independent/4AP-evoked glutamate release. Because 4AP (but not KCI) 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.