VOLTAGE-GATED CALCIUM CURRENTS HAVE 2 OPPOSING EFFECTS ON THE SECRETION OF ALDOSTERONE

Using Ca2+ channel blockers with different specificities for L- and T- type Ca2+ channels, we have investigated the roles of these two channe l types in K+-induced aldosterone secretion. In whole cell voltage-cla mp experiments, the spider toxin omega-agatoxin-IIIA (omega-Aga-IIIA) completely blocks L-type Ca2+ channels but has no effect on T-type Ca2 + channels. In contrast, Ni2+ and 1,4-dihydropyridines block both L- a nd T-type Ca2+ channels. Secretion induced by 7 mM extracellular K+ co ncentration ([K+](o)) is unaffected by omega-Aga-IIIA but is strongly inhibited by Ni2+ or the 1,4-dihydropyridine, nitrendipine. This sugge sts that physiological increases in [K+](o) stimulate aldosterone secr etion primarily by enhancing Ca2+ entry through T-type Ca2+ channels. Surprisingly, secretion induced by 60 mM [K+](o) is enhanced by omega- Aga-IIIA or Ni2+ and is inhibited by the L-type Ca2+ channel activator BAY K 8644. Nitrendipine (1 nM) also stimulates such secretion, altho ugh higher concentrations are inhibitory (concentration inhibiting 50% of maximal response similar to 30 nM). If extracellular Ca2+ concentr ation 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. Togeth er, these results suggest that L-type Ca2+ currents can reduce steroid ogenesis and that the role of these currents was previously misconstru ed because 1,4-dihydropyridines modify secretion by multiple mechanism s. Thus Ca2+ entry can function as a negative modulator of steroid sec retion.