Protein kinase C and the regulation of glutamate exocytosis from cerebrocortical synaptosomes

E T Coffey, T S Sihra, D G Nicholls

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

93 Citeringar (Scopus)


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.

Sidor (från-till)21060-5
Antal sidor6
TidskriftJournal of Biological Chemistry
StatusPublicerad - 5 okt. 1993
MoE-publikationstypA1 Tidskriftsartikel-refererad


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