Silencing GPER abolished the effect of estrogen on peak INa and altered INa kinetics
Having found that GPER affected sodium currents using G1 and G15, we tested whether gene silencing with small interfering RNA (GPER-siRNA, 16.7 nmol/L, 4-6 h) could produce similar results. Knockdown of GPER did not change I NaL in hiPSC-CMs (Figure 7A and C), but it canceled the increase in peak I Na caused by E2 (Figure 7B, D and E). More interestingly, silencing GPER increased the k value of inactivation and decreased the V1/2 values of activation and inactivation (Supplemental Figure 5A and C-F). Unexpectedly, negative GPER-siRNA decreased the V1/2 value of inactivation (Supplemental Figure 5F) and increased the τ value of recovery from inactivation (Supplemental Figure 4A, Supplemental Figure 5B and G). Altogether, these results demonstrated that gene silencing of GPER affected the function of sodium channel. Data of Mean ± S.E.M are presented in supplementary material online, Supplemental Table 1-7.