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.