AENDO May 41/5

Simaan, May, Serge Picard, Jean St-Louis and Michèle Brochu. Functional alteration of dihydropyridinesensitive Ca21 channels in the adrenal glomerulosa of pregnant rats. Am J Physiol Endocrinol Metab 278: E925–E932, 2000.—Our previous work on aldosterone secretion suggested that dihydropyridine-sensitive calcium channels, one type of voltage-dependent calcium channels (VDCC), are functionally impaired in adrenal capsule preparations from the pregnant rat. The aim of this study was to determine whether, during pregnancy, the density and/or activity of these channels is altered in the adrenal zona glomerulosa. These VDCC measured with [3H]nitrendipine binding were not different between membrane preparations of nonpregnant and pregnant rats. Western blots were performed using two different antibodies, a polyclonal (PcAb) directed against the a1subunit of VDCC and a monoclonal (McAb) that recognizes an intracellular domain of that protein. McAb immunoreactivity showed a significant decrease in preparations from pregnant rats, whereas no difference was observed with PcAb. VDCC activity was estimated by 45Ca21 uptake in isolated adrenal cortex and by intracellular calcium concentration ([Ca]i) in adrenal glomerulosa cells with the Ca21 probe fura PE3. These measurements revealed that KCl stimulation produced greater Ca21 influx in nonpregnant than in pregnant rats. Nifedipine (a blocker of VDCC) inhibited this stimulation only in nonpregnant rats, whereas BAY K 8644 (an activator of VDCC) increased Ca21 influx in pregnant rats only. These data suggest that, during pregnancy, the altered regulation of calcium homeostasis in adrenal glomerulosa is linked to a conformational alteration of VDCC.