Pq. Barrett et al., VOLTAGE-GATED CALCIUM CURRENTS HAVE 2 OPPOSING EFFECTS ON THE SECRETION OF ALDOSTERONE, American journal of physiology. Cell physiology, 37(4), 1995, pp. 985-992
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.