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

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Abstract
The effects of oestrogens on action potential and membrane currents were examined in single guinea‐pig atrial myocytes. 17β‐estradiol (3–10 μM) shortened the action potential duration without significant changes in the resting membrane potential. E‐4031 (1 μM) markedly prolonged the action potential duration and induced early afterdepolarization, and 17β‐estradiol (10 μM) 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 Ca2+ currents consisted of both T‐(ICa.T) and L‐type (ICa.L). 17β‐estradiol reduced ICa.L concentration‐dependently, while it (10 μM) suppressed ICa.T only by approximately 10%. 17β‐estradiol did not affect time courses of ICa.L inactivation, but it shifted the steady‐state inactivation curve to more negative potentials. 17β‐estradiol (10 μM) did not affect the time‐dependent K+ current (IK), referred to as IKr and IKs, and inwardly rectifying K+ current. However, 17β‐estradiol (30 μM) or diethylstilbestrol (10 μM) inhibited K+ currents. DES and ethinylestradiol (EES) also suppressed ICa.L, but testosterone and progesterone failed to inhibit ICa.L. The potency of the inhibitory effect on ICa.L was DES>EES>17β‐estradiol. 17β‐estradiol and DES also inhibited the cyclic AMP‐enhanced ICa.L, but cyclic GMP in the pipette or pretreatment of L‐NAME could not block the effects of oestrogen on ICa.L. 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. British Journal of Pharmacology (1999) 127, 429–440; doi:10.1038/sj.bjp.0702576