Inhibition of calcium flux and calcium channel antagonist binding in the PC12 neural cell line by phorbol esters and protein kinase C.

Ca2+- and phospholipid-dependent protein kinase (protein kinase C) has been shown to modify receptor-mediated Ca2+ responses in a variety of cells. To assess its possible role in modulating voltage-dependent Ca2+ responses, we examined the effect of tumor-promoting phorbol esters, which activate protein kinase C, on Ca2+ channel function in the PC12 neural cell line. Phorbol 12-myristate 13-acetate reduced K+-depolarization-evoked 45Ca uptake and decreased binding of the Ca2+ channel antagonist [3H] (+)PN200-110 to intact cells. Inhibition of binding was markedly reduced in PC12 membranes, but was restored by reconstituting membranes with protein kinase C activity. Protein kinase C may therefore participate in endogenous regulation of voltage-dependent Ca2+ channels in mammalian neural cells.