Protein kinase C activator inhibits voltage-sensitive Ca 2+ channels and catecholamine secretion in adrenal chromaffin cells

Abstract

We have investigated the effects of the phorbol ester 12-myristate 13-acetate (PMA) on depolarization-evoked Ca 2+ influx and catecholamine secretion in bovine adrenal chromaffin cells. PMA (100 nM) strongly inhibited K +-evoked [Ca 2+] i transients and Mn 2+ quenching of fura-2 fluorescence. In contrast, 4α-phorbol 12,13-didecanoate, a phorbol ester inactive on protein kinase C (PKC), had no effect. Maximal PMA-mediated inhibition occurred at 5–10 min incubations and were variable from cell to cell, ranging from 25 to 65% of controls. The [Ca 2+] i transients evoked by the L-type Ca 2+ channel activator Bay K 8644 were strongly inhibited by 100 nM PMA. PMA (0.1–10 μM) inhibited K +-evoked adrenaline and noradrenaline release by 23–44%. The data indicate that phorbol ester-mediated activation of PKC inhibits voltage-sensitive Ca 2+ channels in chromaffin cells, leading to a prominent depression of depolarization-evoked catecholamine secretion.