Cardiac toxicity from bisphenol A exposure in human-induced pluripotent stem cell-derived cardiomyocytes

Endocrine-Disrupting Effects of Bisphenol A on the Cardiovascular System: A Review

“…The inhibition of L-type Ca 2+ channels was also shown by Liang et al [ 40 ] in ventricular cells, and by Hyun et al in human-induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs). Moreover, this author also observed that BPA (1–100 µmol/L) inhibited Nav1.5 and hERG channel activity [ 41 ]. More recently, the effect of BPA was compared with BPA substitutes, BPF and BPS; the inhibitory effect on the voltage-gated sodium channel (Nav1.5), L-type voltage-gated Ca 2+ channel (Cav1.2), and the rapidly activating delayed rectifier potassium channel (hERG) was greater for BPA [ 42 ].…”

“…More recently, the effect of BPA was compared with BPA substitutes, BPF and BPS; the inhibitory effect on the voltage-gated sodium channel (Nav1.5), L-type voltage-gated Ca 2+ channel (Cav1.2), and the rapidly activating delayed rectifier potassium channel (hERG) was greater for BPA [ 42 ]. Moreover, we can mention that the effect of BPA on sodium (Na + ) and potassium (K + ) channels has been analyzed previously by other authors [ 41 , 42 , 43 , 44 ].…”

“…The authors exposed the cardiomyocytes to a wide range of BPAs that mimic environmental, clinical, and supraphysiological levels, and showed a reduction in spontaneous beating rate, an increase in heart rate variability (HRV), a reduction in the Ca 2+ transient amplitudes, and prolongation of the Ca 2+ transient upstroke and the duration time [ 50 ]. BPA exposure (1–100 µmol/L) also reduces the Ca 2+ transient rise time and decreases the Ca 2+ transient amplitude of hiPSC-CM in a dose-dependent manner [ 41 ].…”

“…According to these authors, Prudencio et al also recently reported, in 2021, that BPA has a half-maximal inhibitory concentration (IC 50 ) of 55.3 µmol/L and 23.6 µmol/L BPA for fast/peak and late Na + channel currents, respectively, using the same cell type [ 42 ]. In the same year, Ae Hyun et al also demonstrated that BPA (1–100 µmol/L) significantly inhibited sodium current (I Na ) channels (IC 50 = 56.5 µmol/L) [ 41 ]. Using both optical and microelectrode array methodologies, the authors suggested that BPA exposure altered cardiac function in human-induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs), as a slowing of the action potential upstroke (1–100 µmol/L BPA) and a reduction in the action potential amplitude (30–100 µmol/L BPA) were observed.…”

“…Using both optical and microelectrode array methodologies, the authors suggested that BPA exposure altered cardiac function in human-induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs), as a slowing of the action potential upstroke (1–100 µmol/L BPA) and a reduction in the action potential amplitude (30–100 µmol/L BPA) were observed. These alterations may be due to the inhibition of I Na channels [ 41 ]. As recently reviewed by Horváth et al, the late sodium currents’ (I Na , late) inhibitors are potential antiarrhythmic agents.…”