Key Results
Isoproterenol-induced stress increased
peak sodium current and late
sodium current, and shortened action potential duration but the effects
of stress were eliminated by β-Estradiol. Pearson Correlation analysis
demonstrated no association between estrogenic effects on sodium
currents versus content of sodium channel. Activation of GPER produced
similar effects as β-Estradiol, while inhibition of GPER cancelled the
effects induced by β-Estradiol.
Conclusion and Implications
Estrogen through its rapid signal receptor GPER ameliorated the
detrimental effects of β-adrenergic overstimulation like in cardiac
stress on sodium channel dysfunction in hiPSC-CMs. These results are of
great clinical significance as we need to understand the role of sex
hormones in cardiovascular disease.