Protein kinase C mediated regulation of calcium channels in PC-12 pheochromocytoma cells

Depolarization of PC-12 pheochromocytoma cells with K⁺ produces an immediate increase in catecholamine release. The stimulation of release is blocked by Co²⁺, removal of extracellular Ca²⁺ or by dihydropyridine drugs such as nitrendipine. Release is enhanced by other dihydropyridines such as BAY K8644. Release is accompanied by a voltage dependent uptake of ⁴⁵Ca²⁺ which is also blocked by Co²⁺ or nitrendipine and enhanced by BAY K8644. The phorbol ester phorbol 12-myristate-13-acetate (TPA) in the range 10^-9 - 10^-6 M produced little effect by itself but augmented the K⁺ evoked release of catecholamine. An analog of TPA which does not activate protein kinase C was ineffective. In contrast, TPA in the same concentration range blocked influx of ⁴⁵Ca²⁺ induced by 70 mM K⁺ or 70 mM K⁺/ BAY K8644. ⁴⁵Ca²⁺ influx produced by A23187 was not blocked by TPA. The results suggest a system by which protein kinase C may regulate the output of transmitters from secretory cells.