Discussion
This study explored whether estrogen regulates cardiac voltage-gated sodium channel in hiPSC-CMs. Results show that estrogen reduced the increase in peak I Na andI NaL caused by β-adrenergic stimulation via its receptor GPER. Several studies have also used hiPSC-CMs as a cell model to delineate the mechanisms of ion channels and carry out pharmacological research (Portero et al., 2017; T. Yang et al., 2014; Zhao et al., 2018). In addition, hiPSC-CMs exhibited a good physiological response to β-adrenergic stimulation, which provides a unique in vitro simulated cardiac stress model for understanding the estrogenic cardioprotection under stress-induced pathological conditions (Bekhite et al., 2020; Borchert et al., 2017; Zhao et al., 2018). hiPSC-CMs acted abundant expressions of cardiac troponin T (Supplemental Figure 1) and exhibited characteristics similar to native cardiomyocytes (Ma et al., 2011; Zhao et al., 2018) in terms of AP shape and sodium currents, indicating that they are ideal for the purpose of this study.