Fj. Hoffman et Ra. Janis, EFFECTS OF CALCIUM-CHANNEL ANTAGONISTS ON THE PHOSPHORYLATION OF MAJOR PROTEIN-KINASE-C SUBSTRATES IN THE RAT HIPPOCAMPUS, Biochemical pharmacology, 46(4), 1993, pp. 677-681
K+-induced depolarization of rat hippocampal slices resulted in signif
icant increases in the phosphorylation state of myristoylated, alanine
-rich C kinase substrate (MARCKS; also known as 87K, pp80) and neuromo
dulin [also known as growth associated protein 43 (GAP43), B50, F1] as
determined by back-phosphorylation using protein kinase C. The effect
of organic and inorganic Ca2+ antagonists on the phosphorylation of t
hese major protein kinase C substrates in the rat hippocampus was stud
ied to determine whether Ca2+ influx through L- or N-type voltage-sens
itive Ca2+ channels was required for the phosphorylation changes obser
ved. The depolarization-induced changes appeared to be dependent on ex
tracellular Ca2+, based on evidence indicating that the chelation of e
xtracellular Ca2+ with ethylene glycol-bis (beta-amino-ethyl ether)-N,
N,N',N'-tetraacetic acid (EGTA) inhibited these changes. In addition,
pretreatment of the slices with 500 muM Cd2+, but not 300 nM nimodipin
e, 10 muM omega-conotoxin GVIA or 10 muM MK-801, blocked the K+-induce
d change in phosphorylation. These results suggest that K+-induced cha
nges in the phosphorylation of MARCKS and neuromodulin are mediated by
Ca2+-dependent mechanisms other than, or in addition to, those sensit
ive to the organic Ca2+ channel antagonists employed.