EFFECTS OF 17-BETA-ESTRADIOL ON EARLY AFTERDEPOLARIZATIONS AND L-TYPECA2-1 IN GUINEA-PIG PAPILLARY-MUSCLES AND VENTRICULAR MYOCYTES( CURRENTS INDUCED BY ENDOTHELIN)

By use of standard microelectrodes and whole cell patch clamp, the eff ects of 17 beta-estradiol on early afterdepolarizations (EADs) and inc rease of L-type Ca2+ currents (L-I-Ca) induced by endothelin-1 (ET-1) were studied in guinea pig ventricular papillary muscles and myocytes. The results indicated that superfusion with ET-1 for 30 min resulted in a marked prolongation of the action potential duration (APD) and ca used stable EADs leading to triggered activity occurring at the platea u of the action potentials in isolated guinea pig ventricular papillar y muscles. With the addition of 17 beta-estradiol (30 mu mol/l), APD w as shortened and EADs were decreased In the patch clamp study, ET-1 in duced an increase of mean peak L-I-Ca from 534.46 +/- 46.23 to 1003.15 +/- 39.12 (pA) with the peak voltage-current curve shifting to the le ft. When 17 beta-estradiol (30 mu mol/l) was added, the L-I-Ca was dec reased by Lip to 33.32% (p < 0.01) with the peak voltage-current curve shifting to the right. In contrast to the steady-state inactivation c urve, ET-1 shifted the steady-state activation curve ill the depolariz ation direction. However; with the addition of 17 beta-estradiol, the deviation of the steady-state activation and inactivation curves cause d by ET-1 was suppressed. In conclusion, 17 beta-estradiol appears to attenuate the prolongation of APD and reduce EADs induced by ET-1 in g uinea pig papillary muscles by its inhibitory effect oil L-I-Ca.