Antiarrhythmic effect and its underlying ionic mechanism of 17β-estradiol in cardiac myocytes

1 The effects of oestrogens on action potential and membrane currents were examined in single guinea-pig atrial myocytes. 2 17 beta-estradiol (3-10 mu M) Shortened the action potential duration without significant changes in the resting membrane potential. E-4031 (1 mu M) markedly prolonged the action potential duration and induced early afterdepolarization, and 17 beta-estradiol (10 mu M) abolished it. 3 When cells were perfused in isoproterenol-containing solution, action potentials due to abnormal automaticity caused by membrane depolarization developed, and were also inhibited by 17 beta-estradiol. 4 Under voltage clamp conditions, the voltage-dependent Ca2+ currents consisted of both T-(I-Ca.T) and L-type (I-Ca.L). 17 beta-estradiol reduced I-Ca.L concentration-dependently, while it (10 mu M) suppressed I-Ca.T only by approximately 10%. 17 beta-estradiol did not affect time courses of I-Ca.L inactivation, but it shifted the steady-state inactivation curve to more negative potentials. 5 17 beta-estradiol (10 mu M) did not affect the time-dependent K+ current (IK), referred to as IK, and I-Ks, and inwardly rectifying K+; current. However, 17 beta-estradiol (30 mu M) or diethylstilbestrol (10 mu M) inhibited Ki currents. 6 DES and ethinylestradiol (EES) also suppressed I-Ca.L but testosterone and progesterone failed to inhibit I-Ca.L The potency of the inhibitory effect on I-Ca.L was DES > EES > 17 beta-estradiol. 7 17 beta-estradiol and DES also inhibited the cyclic AMP-enhanced I-Ca.L, but cyclic GMP in the pipette or pretreatment of L-NAME could not block the effects of oestrogen on I-Ca.L 8 These results suggest that oestrogen specifically has antiarrhythmic effects, possibly by acting the L-type Ca2+ channels. The antiarrhythmic effects of oestrogens may contribute to the cardioprotective actions of oestrogens.