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 17 beta-estradiol (10-30 mu M) 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 mu M 17 beta-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 mu M 17 beta-estradiol the peak inward Ca2+ 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 mu M 17 beta-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 17 beta-estradiol prolonged APD mainly by inhibiting the I-K components I-Kr and I-Ks.