Ca2+ channels and aldosterone secretion: modulation by K+ and atrial natriuretic peptide.
Two populations of voltage-dependent Ca2+ channels, T-type and L-type, are present in bovine adrenal glomerulosa cells. Activation of these channels by cell depolarization with the resultant increase in Ca2+ influx may be one way in which agonists regulate aldosterone secretion. In addition, these channels may be the site of antagonist action. In the present study, we have demonstrated that atrial natriuretic peptide (ANP), an antagonist of aldosterone secretion, alters only the voltage dependence of inactivation of the T-type channel while enhancing the voltage dependence of activation of a subpopulation of L-type channels. These patch-clamp data, which demonstrated contrasting effects of ANP on the activity of T- and L-type Ca2+ channels correlated with changes induced in cytosolic calcium [( Ca2+]i). In the weakly depolarized cell, ANP (greater than 30 pM) lowered [Ca2+]i, in contrast to the strongly depolarized cell, in which ANP (greater than 10 pM) raised [Ca2+]i. Similar alterations in the level of [Ca2+]i in the stimulated cell were induced by the Ca(2+)-channel blocker nitrendipine and the L-type channel agonist, (-)BAY K 8644. With increasing concentrations of extracellular K+ (3.5-60 mM) the rate of aldosterone secretion rose nonmonotonically. ANP inhibited secretion over this broad range of K+ concentrations; however, its potency as an inhibitor of secretion was diminished in the strongly depolarized cell. These data are discussed in the context of a model that proposes a role for sustained Ca2+ influx in cell activation.
Barrett
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PQ
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Isales
C M
CM
Bollag
W B
WB
McCarthy
R T
RT
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D004594:Electrophysiology; D009568:Nitrendipine / Q000494:pharmacology; D009994:Osmolar Concentration; D011188:Potassium / Q000494:pharmacology*; D015384:Zona Glomerulosa / Q000166:cytology / Q000378:metabolism*
D015220:Calcium Channels; D000450:Aldosterone; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009320:Atrial Natriuretic Factor; D009568:Nitrendipine; D011188:Potassium; D002118:Calcium