EFFECTS OF CALCIUM-CHANNEL ANTAGONISTS ON THE PHOSPHORYLATION OF MAJOR PROTEIN-KINASE-C SUBSTRATES IN THE RAT HIPPOCAMPUS

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.