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.