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

The effects of oestrogens on action potential and membrane currents were examined in single guinea‐pig atrial myocytes. 17β‐estradiol (3–10 μ M ) shortened the action potential duration without significant changes in the resting membrane potential. E‐4031 (1 μ M ) markedly prolonged the action potential duration and induced early afterdepolarization, and 17β‐estradiol (10 μ M ) abolished it. When cells were perfused in isoproterenol‐containing solution, action potentials due to abnormal automaticity caused by membrane depolarization developed, and were also inhibited by 17β‐estradiol. Under voltage clamp conditions, the voltage‐dependent Ca 2+ currents consisted of both T‐(I Ca.T ) and L‐type (I Ca.L ). 17β‐estradiol reduced I Ca.L concentration‐dependently, while it (10 μ M ) suppressed I Ca.T only by approximately 10%. 17β‐estradiol did not affect time courses of I Ca.L inactivation, but it shifted the steady‐state inactivation curve to more negative potentials. 17β‐estradiol (10 μ M ) did not affect the time‐dependent K + current (I K ), referred to as I Kr and I Ks , and inwardly rectifying K + current. However, 17β‐estradiol (30 μ M ) or diethylstilbestrol (10 μ M ) inhibited K + currents. 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>17β‐estradiol. 17β‐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 . These results suggest that oestrogen specifically has antiarrhythmic effects, possibly by acting the L‐type Ca 2+ channels. The antiarrhythmic effects of oestrogens may contribute to the cardioprotective actions of oestrogens.British Journal of Pharmacology (1999) 127 , 429–440; doi: 10.1038/sj.bjp.0702576