An ion channel locus for the protein kinase C potentiation of transmitter glutamate release from guinea pig cerebrocortical synaptosomes.
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. 4 beta-Phorbol dibutyrate (4 beta-PDBu) enhances the Ca(2+)-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 Ca(2+)-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.
Barrie
A P
AP
Department of Biochemistry, University of Dundee, Scotland, U.K.
Nicholls
D G
DG
Sanchez-Prieto
J
J
Sihra
T S
TS
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D004594:Electrophysiology; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006168:Guinea Pigs; D007473:Ion Channels / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D013574:Synaptosomes / Q000378:metabolism* / Q000502:physiology
D005971:Glutamates; D007473:Ion Channels; D018377:Neurotransmitter Agents; D015240:Phorbol 12,13-Dibutyrate; D018698:Glutamic Acid; D011189:Potassium Chloride; D015761:4-Aminopyridine; D011493:Protein Kinase C