Et. Coffey et al., PROTEIN-KINASE-C AND THE REGULATION OF GLUTAMATE EXOCYTOSIS FROM CEREBROCORTICAL SYNAPTOSOMES, The Journal of biological chemistry, 268(28), 1993, pp. 21060-21065
The role of protein kinase C (PKC) in the regulation of transmitter gl
utamate release from rat cerebral cortical synaptosomes is investigate
d. Two depolarization protocols are used: first, elevated KCl, which p
roduces a clamped depolarization, and second, 4-aminopyridine, which e
vokes spontaneous ''action potentials'' allowing any potential modulat
ion of Na+ or K+ channels to influence release. Although the PKC inhib
itor Ro 31-8220 prevents both the depolarization-evoked and phorbol di
butyrate (PDBu)-evoked phosphorylation of the major presynaptic PKC su
bstrate, myristoylated alanine-rich C kinase substrate, it is without
effect on KCl-evoked Ca2+-dependent glutamate release. Ro 31-8220 tota
lly inhibits the Ca2+-dependent 4-aminopyridine-evoked release of glut
amate in the presence and absence of PDBu and again decreases the phos
phorylation of myristoylated alanine-rich C kinase substrate. Ro 31-82
20 strongly inhibits the 4-aminopyridine-evoked increase in [Ca2+] bot
h in the presence and absence of PDBu and antagonizes the PDBu enhance
ment of depolarization. This indicates that PKC isoforms activatable b
y PDBu and sensitive to Ro 31-8220 play no discernable role in Ca2+-se
cretion coupling per se in cerebral cortical glutamatergic nerve termi
nals, but that the kinase plays a major role in regulating the depolar
ization of the terminal.