Catecholamine secretion induced by tetraethylammonium from cultured bovine adrenal chromaffin cells.
The resting potential in adrenal medullary chromaffin cells is maintained by the activity of different K(+)-channels. Blockade of K(+)-channels should, at least in principle, lead to membrane depolarization, and the ensuing activation of voltage-gated Ca(2+)-channels should promote Ca2+ entry and catecholamine (CA) secretion. In support of this mechanism we found and report here that the K(+)-channel blocker tetraethylammonium (TEA) depolarized the chromaffin cell membrane, induced a substantial elevation in cytosolic [Ca2+], and a dose-dependent CA secretion reaching 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 dependent on [Ca2+]o. In the presence of [Ca2+]o, TEA-stimulated CA release was blocked completely by elevated [MgCl2]o (12 mM), and inhibited in part by the Ca(2+)-channel antagonist nifedipine. The Ca(2+)-channel agonist Bay K-8644 markedly enhanced TEA-evoked CA release suggesting the involvement of L-type Ca(2+)-channels. Since, external application of TEA (30-50 mM) markedly blocked outward K+ currents but not inward currents carried by Na+ and Ca2+, we concluded that TEA stimulates CA secretion by blocking those K(+)-channels involved in the maintenance of the resting membrane potential.
Laboratory of Cell Biology and Genetics, NIDDK, National Institutes of Health, Bethesda, MD 20892.
C
C
González-García
V
V
Ceña
H R
HR
Keiser
E
E
Rojas
D000313:Adrenal Medulla / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D004095:Dihydropyridines / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology*
D015220:Calcium Channels; D002395:Catecholamines; D004095:Dihydropyridines; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D002118:Calcium