Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2025
Atrial arrhythmogenesis and electrophysiological remodeling in hypokalaemic metabolic syndrome: the role of apamin-sensitive SK channels.
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Kuo Chia-Hao, Shih Jo-Yun, Lin Yi-Hsiung, Chang Chien-Wei, Jhuo Shih-Jie, Lin Tzu-Chieh, Huang Tien-Chi, Liu I Hsin, Kao Pei-Heng, Lin En-Ying, Huang Pin-Chieh, Chen Xin-Hui, Chen Chao-Yi, Feng Yu-Chen, Zheng Ying-Xuan, Lin Min-Huei, Chen Guan-Lin, Hsu Po-Chao, Lee Chien-Hung, Wu Chun-Chieh, Lee Hsiang-Chun, Wu Bin-Nan, Lin Shien-Fong, Lai Wen-Ter, Tsai Wei-Chung
Аннотация
AIMS: Metabolic syndrome (MetS) increases the risk of atrial arrhythmias (AA). Hypokalaemia, often secondary to diuretics or diet, frequently coexists with MetS and influences calcium handling. This study investigates the role of apamin-sensitive small-conductance calcium-activated potassium (SK) channels in atrial arrhythmogenesis under hypokalaemic MetS conditions.
METHODS AND RESULTS: High-fat diets (HFD) were fed to mice at 8 weeks old for 16 weeks to mimic MetS. SK current was measured via voltage clamp, and Kcnn1-Kcnn3/CACNA1S, CACNA1C, and CACNA1D expression was assessed by qRT-PCR. We used optical mapping of intact mice hearts to assess the atrial action potential duration (APD), calcium transient duration (CaTD), conduction velocity (CV), conduction vector standard deviation, and AA inducibility in mice during hypokalaemia. HFD mice showed increased SK current and Kcnn3 expression. Apamin prolonged APD significantly in HFD mice. The APD heterogeneity of HFD was higher than that of the control mice. APD alternans threshold was significantly increased after apamin administration in HFD than that in control mice. Heterogeneity of conduction vectors in HFD is greater than that in control mice after apamin application. After apamin injection, AA inducibility is higher in HFD than that in control mice. AA inducibility was higher after apamin application in HFD, where AA was successfully induced.
CONCLUSION: Our study demonstrated that apamin-sensitive SK channels may exert an antiarrhythmic effect in a hypokalaemic heart of the MetS model. These findings underscore the importance of evaluating the potential risks associated with the use of SK channel blockers in patients with hypokalaemic MetS.
METHODS AND RESULTS: High-fat diets (HFD) were fed to mice at 8 weeks old for 16 weeks to mimic MetS. SK current was measured via voltage clamp, and Kcnn1-Kcnn3/CACNA1S, CACNA1C, and CACNA1D expression was assessed by qRT-PCR. We used optical mapping of intact mice hearts to assess the atrial action potential duration (APD), calcium transient duration (CaTD), conduction velocity (CV), conduction vector standard deviation, and AA inducibility in mice during hypokalaemia. HFD mice showed increased SK current and Kcnn3 expression. Apamin prolonged APD significantly in HFD mice. The APD heterogeneity of HFD was higher than that of the control mice. APD alternans threshold was significantly increased after apamin administration in HFD than that in control mice. Heterogeneity of conduction vectors in HFD is greater than that in control mice after apamin application. After apamin injection, AA inducibility is higher in HFD than that in control mice. AA inducibility was higher after apamin application in HFD, where AA was successfully induced.
CONCLUSION: Our study demonstrated that apamin-sensitive SK channels may exert an antiarrhythmic effect in a hypokalaemic heart of the MetS model. These findings underscore the importance of evaluating the potential risks associated with the use of SK channel blockers in patients with hypokalaemic MetS.