Functional alteration of dihydropyridine-sensitive Ca2+ channels in the adrenal glomerulosa of pregnant rats

Our previous work on aldosterone secretion suggested that dihydropyridine-s ensitive calcium channels, one type of voltage-dependent calcium channels ( VDCC), are functionally impaired in adrenal capsule preparations from the p regnant rat. The aim of this study was to determine whether, during pregnan cy, the density and/or activity of these channels is altered in the adrenal zona glomerulosa. These VDCC measured with [H-3]nitrendipine binding were not different between membrane preparations of nonpregnant and pregnant rat s. Western blots were performed using two different antibodies, a polyclona l (PcAb) directed against the alpha(1)-subunit of VDCC and a monoclonal (Mc Ab) that recognizes an intracellular domain of that protein. McAb immunorea ctivity showed a significant decrease in preparations from pregnant rats, w hereas no difference was observed with PcAb. VDCC activity was estimated by Ca-45(2+) uptake in isolated adrenal cortex and by intracellular calcium c oncentration ([Ca2+](i)) in adrenal glomerulosa cells with the Ca2+ probe f ura PE3. These measurements revealed that KCI stimulation produced greater Ca2+ influx in nonpregnant than in pregnant rats. Nifedipine (a blocker of VDCC) inhibited this stimulation only in nonpregnant rats, whereas BAY K 86 44 tan activator of VDCC) increased Ca2+ influx in pregnant rats only. Thes e data suggest that, during pregnancy, the altered regulation of calcium ho meostasis in adrenal glomerulosa is linked to a conformational alteration o f VDCC.