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Endotoxin modulates the electrophysiological characteristics of human embryonic stem cell-differentiated cardiomyocytes |
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| Authors: | Shiji Wang Yu Wang Xin Guo Yingji Li Li Yan Chengxi Wei Ming Zhao |
| Institution: | 1. First Hospital of Jilin University, Changchun, Jilin, China
These authors have contributed equally to this work.;2. Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia, China Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, Inner Mongolia, China These authors have contributed equally to this work.;3. Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia, China Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, Inner Mongolia, China;4. Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia, China |
| 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 Ik channel currents were 1.254 µg/ml. LPS-treated HIPSC-CMs showed a lower sodium channel current, L-type calcium channel current, and Ik 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 Ik channel currents. These results suggest a potential mechanism of cardiomyocyte injury in endotoxemia. |
| Keywords: | arrhythmia delayed rectifier potassium channel show activation current lipopolysaccharide (LPS) L-type calcium current sodium current |