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

Previous studies have shown that 17 beta-estradiol (beta-E(2)) has a d irect acute inhibitory effect on vascular smooth muscle (VSM) contract ion. To investigate the mechanisms underlying this phenomenon, we util ized 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 protoc ols in A7r5 cultured VSMC. T-type current, inactivated in < 100 ms, wa s reduced by Ba2+ and was comparatively little affected by isradipine. L-type current required higher voltages to activate, inactivated slow ly, was greatly increased by Ba2+, and could be completely inhibited b y 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 alph a-E(2) (a hormonally inactive isomer of estradiol) caused significantl y 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.