Abstract
The role of protein kinase C (PKC) in the regulation of transmitter glutamate release from rat cerebral cortical synaptosomes is investigated. Two depolarization protocols are used: first, elevated KCl, which produces a clamped depolarization, and second, 4-aminopyridine, which evokes spontaneous "action potentials" allowing any potential modulation of Na+ or K+ channels to influence release. Although the PKC inhibitor Ro 31-8220 prevents both the depolarization-evoked and phorbol dibutyrate (PDBu)-evoked phosphorylation of the major presynaptic PKC substrate, myristoylated alanine-rich C kinase substrate, it is without effect on KCl-evoked Ca(2+)-dependent glutamate release. Ro 31-8220 totally inhibits the Ca(2+)-dependent 4-aminopyridine-evoked release of glutamate in the presence and absence of PDBu and again decreases the phosphorylation of myristoylated alanine-rich C kinase substrate. Ro 31-8220 strongly inhibits the 4-aminopyridine-evoked increase in [Ca2+] both in the presence and absence of PDBu and antagonizes the PDBu enhancement of depolarization. This indicates that PKC isoforms activatable by PDBu and sensitive to Ro 31-8220 play no discernable role in Ca(2+)-secretion coupling per se in cerebral cortical glutamatergic nerve terminals, but that the kinase plays a major role in regulating the depolarization of the terminal.
Original language | English |
---|---|
Pages (from-to) | 21060-5 |
Number of pages | 6 |
Journal | Journal of Biological Chemistry |
Volume | 268 |
Issue number | 28 |
Publication status | Published - 5 Oct 1993 |
MoE publication type | A1 Journal article-refereed |
Keywords
- 4-Aminopyridine/pharmacology
- Animals
- Calcium/metabolism
- Cerebral Cortex/cytology
- Exocytosis
- Glutamates/metabolism
- Glutamic Acid
- Indoles/pharmacology
- Intracellular Signaling Peptides and Proteins
- Male
- Membrane Potentials
- Membrane Proteins
- Myristoylated Alanine-Rich C Kinase Substrate
- Phorbol 12,13-Dibutyrate/pharmacology
- Phosphorylation
- Potassium Channels/drug effects
- Potassium Chloride/pharmacology
- Protein Kinase C/antagonists & inhibitors
- Proteins/metabolism
- Rats
- Rats, Wistar
- Sodium Channels/drug effects
- Synaptosomes/drug effects