Voltage-gated calcium currents have two opposing effects on the secretion
of aldosterone.
Barrett, P. Q., E. A. Ertel, M. M. Smith, J. J. Nee, and C. J. Cohen.
Department of Pharmacology, University of Virginia, Charlottesville, VA
22908 Department of Membrane Biochemistry and Biophysics, Merck Research
Laboratories, Rahway, NJ 07065.
APStracts 2:0002C, 1995.
Using Ca channel blockers with different specificities for L- and T-type Ca
channels, we have investigated the roles of these two channel types in
potassium-induced aldosterone secretion. In whole-cell voltage clamp
experiments, the spider toxin Omega-Aga-IIIA completely blocks L-type Ca
channels but has no effect on T-type Ca channels. In contrast, Ni2+ and 1,4
-dihydropyridines block both L- and T-type Ca channels. Secretion induced by 7
mM [K+]o is unaffected by Omega-Aga-IIIA but it is strongly inhibited
by Ni2+ or the 1,4-dihydropyridine, nitrendipine. This suggests that
physiological increases in [K+]o stimulate aldosterone secretion
primarily by enhancing Ca entry through T-type Ca channels. Surprisingly,
secretion induced by 60 mM [K+]o is enhanced by Omega-Aga-IIIA or Ni2+
and it is inhibited by the L-type Ca channel activator BAY K 8644. 1 nM
nitrendipine also stimulates such secretion, although higher concentrations
are inhibitory (IC50 nearly equal to 30 nM). If [Ca2+]o is reduced from 1.25
to 0.5 mM, secretion induced by 60 mM [K+]o is enhanced, and Ni2+ or low
nitrendipine become inhibitory. Together, these results suggest that L-type
Ca currents can reduce steroidogenesis and that the role of these currents
was previously misconstrued because 1,4-dihydropyridines modify secretion by
multiple mechanisms. Thus, Ca entry can function as a negative modulator of
steroid secretion.
Received 1 July 1994; accepted in final form 17 October 1994
APS Manuscript Number C376-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1994 The American Physiological Society.
Published in APStracts on 27 February 1995.