17-BETA-ESTRADIOL ATTENUATES VOLTAGE-DEPENDENT CA2+ CURRENTS IN A7R5 VASCULAR SMOOTH-MUSCLE CELL-LINE

Previous studies have shown that 17 beta-estradiol (beta-E(2)) has a direct acute inhibitory effect on vascular smooth muscle (VSM) contraction. To investigate the mechanisms underlying this phenomenon, we utilized whole cell patch-clamping techniques to study effects of beta-E(2) on voltage-dependent Ca2+ channels in cultured VSM cells (VSMC). T- and L-type Ca2+ currents were characterized with ramp and pulse protocols in A7r5 cultured VSMC. T-type current, inactivated in < 100 ms, was reduced by Ba2+ and was comparatively little affected by isradipine. L-type current required higher voltages to activate, inactivated slowly, was greatly increased by Ba2+, and could be completely inhibited by 5 mu M isradipine. beta-E(2) (10 mu M) significantly reduced peak L-type Ba2+ current and T-type Ca2+ current within 1-2 min, whereas alpha-E(2) (a hormonally inactive isomer of estradiol) caused significantly less reduction in both types of current. Vehicle (0.1% ethanol) had no significant effect on either current. The inhibitory effect of beta-E(2) on voltage-dependent Ca2+ currents may contribute to previously demonstrated beta-E(2) attenuation of VSM contraction.