Estrogen increased peak INa but reduced both of INaL and peak INa after stress
Some studies have shown that estrogen exert concentration-dependent dual effects on ventricular electrical activity in guinea pigs (Kurokawa, Kodama, Clancy, & Furukawa, 2016; Kurokawa et al., 2008). To test the rapid effect of estrogen on sodium channel and whether it is dependent on concentration, hiPSC-CMs were cultured with low, medium, and high concentrations of estrogen for 1 hour. In our study, estrogen did not alter I NaL at any concentration under normal condition. In contrast, under stress state, estrogen at medium concentration inhibited I NaL and this effect was not observed for the low and high concentrations. Estrogen increased peak I Na at all concentrations, but reduced the augmentation in peak I Na at medium concentration under stress state. Estrogen did not affect activation, inactivation and recovery from inactivation of sodium channel under stress or basal state. Although previous studies have revealed gender specific differences in peak I Na andI NaL, the effect of estrogen on those sodium currents is still unclear. Therefore, our results further complement the role of sex hormone in regulating sodium currents, and suggest for the first time that estrogen blunts the increase in sodium currents caused by β-adrenergic overstimulation.