Effects of estradiol on cardiac ion channel currents

Steroids are known to exert direct and indirect effects on cardiovascular functions, and women have been found to be more susceptible to QT prolongation than men. Although many clinical studies have been performed, the effects of steroids on cardiac repolarization are not yet fully understood. We examined the effects of 17-beta-estradiol (estradiol) on the major cardiac currents that are correlated to clinical observations of arrhythmias. Effects on the two major currents responsible for repolarization of the cardiac action potential (mediated by the human ether-à-gogo related gene (HERG) product), and by the potassium channel Q1 (KCNQ1) co-expressed with the potassium channel accessory subunit E1 (KCNE1) were examined, as well as effects on the sodium inward current (mediated by the sodium channel 5A (SCN5A) and generating the rapid upstroke of the action potential). A concentration-dependent effect of estradiol on the KCNQ1/KCNE1-mediated potassium current was observed. The half-maximal inhibition concentration (IC50) of estradiol on the KCNQ1/KCNE1 ion channel was calculated to 1.13 ± 0.23 μM. The HERG-mediated potassium and the SCN5A-mediated sodium currents, however, were only slightly reduced by estradiol at concentrations of up to 30 μM. This suggests that alterations of the cardiac action potentials by steroids may be mediated by interaction with the KCNQ1/KCNE1 ion channel.