Differential control of tyrosine hydroxylase activation and catecholamine secretion by voltage-operated Ca2+ channels in bovine chromaffin cells

Contributions of L-, N-, and P/Q-type voltage-operated Ca2+ channels to two responses of bovine adrenal chromaffin cells have been studied using the n onreceptor stimulus K+ depolarization. Tyrosine hydroxylase activity and ca techolamine secretion were both increased by K+ over a similar concentratio n range and in a Ca2+-dependent manner. At a submaximal concentration of 20 mM K+, tyrosine hydroxylase activation was reduced by nitrendipine but una ffected individually by (+/-)-Bay K 8644, omega-conotoxin GVIA, omega-agato xin IVA, and omega-conotoxin MVIIC. It was fully blocked by combined inhibi tion of L-, N-, and P/Q-type channels. With a maximal concentration of 50 m M K+, tyrosine hydroxylase activation was unaffected by nitrendipine as wel l as by each of the other drugs on its own; however, it was reduced by 71 % by combined inhibition of L-, N-, and P/Q-type channels. In contrast, cate cholamine secretion with both 20 and 50 mM K+ was enhanced by (+/-)-Bay K 8 644, partially inhibited by nitrendipine and omega-conotoxin MVIIC, and com pletely blocked by a combination of antagonists for L-, N-, and P/Q-type ch annels. The results show that Ca2+ entry through voltage-operated Ca2+ chan nels can differentially regulate distinct chromaffin cell responses and tha t this is an intrinsic property of the mechanisms by which Ca2+ entry activ ates these responses. It is not dependent on the parallel activation of oth er signaling events by receptors.