中国病理生理杂志2025，Vol.41Issue(5)：895-901,7.DOI:10.3969/j.issn.1000-4718.2025.05.007
TWIK-1通道在低血钾诱发人心肌细胞异常起搏活动中的作用及其机制
Effect of TWIK-1 channel on hypokalemia-induced abnormal pacemaker activities in human cardiomyocytes and its mechanisms
摘要
Abstract
AIM:This study aims to investigate the impact of TWIK-1 channels on abnormal pacemaker activi-ties induced by hypokalemia and to elucidate the underlying mechanisms.METHODS:The gene sequences encoding hu-man TWIK-1,specific TWIK-1 shRNA and TWIK-1-T118i mutant were synthesized and subsequently subcloned into lenti-viral vectors.To knock down the TWIK-1 gene in human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs),the cells were transduced with lentivirus carrying the specific TWIK-1 shRNA sequences.For the overexpression of TWIK-1 or the TWIK-1-T118i mutant in HL-1 mouse cardiomyocytes,the cells received lentiviral transduction containing the respective gene sequences.Patch-clamp techniques were employed to assess the effects of 1 mmol/L extracellular K+on the membrane potentials and whole-cell currents of the cardiomyocytes.RESULTS:Under conditions of 1 mmol/L extra-cellular K+,depolarization of membrane potentials was observed in the hiPSC-CMs and the HL-1 mouse cardiomyocytes ex-pressing human TWIK-1 channel,leading to the induction of abnormal pacemaker activities.This phenomenon could be reversibly abolished by the removal of extracellular Na+or inhibited through TWIK-1 knockdown.In contrast,the mem-brane potentials of HL-1 mouse cardiomyocytes expressing human TWIK-1-T118i mutant hyperpolarized,with no occur-rence of abnormal pacemaker activities.The hiPSC-CMs exhibiting abnormal pacemaker activities at 1 mmol/L extracellu-lar K+demonstrated TWIK-1-like Na+leak currents,which were blocked by quinine,a non-selective blocker of TWIK-1.CONCLUSION:The TWIK-1 channels play a critical role in the development of hypokalemia-induced abnormal pace-maker activities in human cardiomyocytes by facilitating Na+leak currents.关键词
TWIK-1双孔钾通道/低钾血症/心肌细胞/异常起搏活动Key words
TWIK-1 two-pore potassium channels/hypokalemia/cardiomyocytes/abnormal pacemaker ac-tivities分类
临床医学引用本文复制引用
张恒羲,熊蕾,巫悦,吕金花,左征,李若兰,张德绸,刘平,左东川..TWIK-1通道在低血钾诱发人心肌细胞异常起搏活动中的作用及其机制[J].中国病理生理杂志,2025,41(5):895-901,7.基金项目
国家自然科学基金资助项目(No.81800303) （No.81800303）
四川省自然科学基金(No.2024NSFSC2103 （）
No.2022YFS0613) （）
西南医科大学大学生创新创业训练计划项目(No.S202210632293 （）
No.S202310632176) （）
