CATECHOLAMINE SECRETION INDUCED BY TETRAETHYLAMMONIUM FROM CULTURED BOVINE ADRENAL CHROMAFFIN CELLS

The resting potential in adrenal medullary chromaffin cells is maintai ned by the activity of different K+-channels. Blockade of K+-channels should, at least in principle, lead to membrane depolarization, and th e ensuing activation of voltage-gated Ca2+-channels should promote Ca2 + entry and catecholamine (CA) secretion. In support of this mechanism we found and report here that the K+-channel blocker tetraethylammoni um (TEA) depolarized the chromaffin cell membrane, induced a substanti al elevation in Cytosolic [Ca2+], and a dose-dependent CA secretion re aching a maximum at 50 mM of approx. 10% of the total CA in the cells. In addition, TEA-induced CA secretion was found to be absolutely depe ndent on [Ca2+]o. In the presence of [Ca2+]o, TEA-stimulated CA releas e was blocked completely by elevated [MgCl2]o (12 mM), and inhibited i n part by the Ca2+-channel antagonist nifedipine. The Ca2+-channel ago nist Bay K-8644 markedly enhanced TEA-evoked CA release suggesting the involvement of L-type Ca2+-channels. Since, external application of T EA (30-50 mM) markedly blocked outward K+ currents but not inward curr ents carried by Na+ and Ca2+, we concluded that TEA stimulates CA secr etion by blocking those K+-channels involved in the maintenance of the resting membrane potential.