Effects of estrogen on action potential and membrane currents in guinea pig ventricular myocytes

To explore a possible ionic basis for the prolonged Q-T interval in women compared with that in men, we investigated the electrophysiological effects of estrogen in isolated guinea pig ventricular myocytes. Action potentials and membrane currents were recorded using the whole cell configuration of the patch-clamp technique. Application of 17beta-estradiol (10-30 microM) significantly prolonged the action potential duration (APD) at 20% (APD(20)) and 90% repolarization (APD(90)) at stimulation rates of 0. 1-2.0 Hz. In the presence of 30 microM 17beta-estradiol, APD(20) and APD(90) at 0.1 Hz were prolonged by 46.2 +/- 17.1 and 63.4 +/- 11.7% of the control (n = 5), respectively. In the presence of 30 microM 17beta-estradiol the peak inward Ca(2+) current (I(CaL)) was decreased to 80.1 +/- 2.5% of the control (n = 4) without a shift in its voltage dependence. Application of 30 microM 17beta-estradiol decreased the rapidly activating component of the delayed outward K(+) current (I(Kr)) to 63.4 +/- 8% and the slowly activating component (I(Ks)) to 65.8 +/- 8.7% with respect to the control; the inward rectifier K(+) current was barely affected. The results suggest that 17beta-estradiol prolonged APD mainly by inhibiting the I(K) components I(Kr) and I(Ks).