Endotoxin modulates the electrophysiological characteristics of human embryonic stem cell‐differentiated cardiomyocytes

内毒素调节人类胚胎干细胞分化的心肌细胞的电生理特性

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Abstract

Gram‐negative bacteria‐induced infections result in fever, arrhythmia, and even death. Lipopolysaccharide (LPS), a constituent of bacteria, leads to an inflammatory response under sepsis and increase arrhythmogenesis. This study analyzed the effects on human embryonic stem cell‐differentiated cardiomyocytes (HIPSC‐CMs) exposed to LPS. A whole cell patch clamp was used to record the action potential (AP) and ionic currents with or without different doses of LPS in HIPSC‐CMs. Compared with the control, a different dose (0.04, 0.2, 1, and 5 µg/ml) of LPS‐treated HIPSC‐CMs resulted in a longer AP duration. The IC50 of sodium channel current was 1.254 µg/ml, L‐type calcium channel current was 5 µg/ml, and I(k) channel currents were 1.254 µg/ml. LPS‐treated HIPSC‐CMs showed a lower sodium channel current, L‐type calcium channel current, and I(k) channel currents. Furthermore, the expressions of Nav1.5 were decreased, and L‐Ca, Kv11.1, and Kv7.1 were increased in LPS‐treated HIPSC‐CMs. LPS‐induced arrhythmogenesis was related to the electrophysiological characteristics of sodium channel current, L‐type calcium channel current, and I(k) channel currents. These results suggest a potential mechanism of cardiomyocyte injury in endotoxemia.

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