Estrogen normalized action potential parameters of hiPSC-CMs under stress conditions
To assess the effect of E2 on electrophysiological function of hiPSC-CMs, we recorded APs of cells exposed to ISO under various concentrations of E2. Representative APs and slope curves of hiPSC-CMs are shown (Figure 4A). Notably, E2 (1 nmol/L and 100 nmol/L) decreased AP amplitude (APA) in hiPSC-CMs (Figure 4B). E2 (100 nmol/L) decreased resting membrane potential (RMP) (Figure 4C). Moreover, E2 at all concentrations decreased maximal action potential upstroke velocity (dV /dt max) (Figure 4D). In addition, action potential duration at 50% repolarization (APD50) and action potential duration at 90% repolarization (APD90) were prolonged by 1 nmol/L E2 (Figure 4E-G). In contrast, ISO stimulation decreased APA, dV /dt max and shortened action potential duration at 10% repolarization (APD10),APD50 and APD90 but had no effect on RMP (Figure 1K-Q). In cells treated with ISO, E2 had no effects on APA, dV /dt max and APD10 (Figure 4H, J and K). In comparison, E2 prolonged APD50 (at only 100 nmol/L) and APD90(Figure 4L and M). Interestingly, although E2 at 0.01 nmol/L and 1 nmol/L had no effect on RMP, they markedly decreased RMP under stress state (Figure 4C and I). Complete data on Mean ± S.E.M are provided in supplementary material online, Supplemental Table 8.