ArticleCirculation2015
Small-Conductance Calcium-Activated Potassium Current Is Activated During Hypokalemia and Masks Short-Term Cardiac Memory Induced by Ventricular Pacing.
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Article in Circulation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 43 citations in OpenAlex.
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- Antiarrhythmic effects of mirabegron on ventricular fibrillation in Langendorff-perfused rabbit ventricles.The Journal of physiology · 2025Article
- Sequence-Dependent Repolarization Is Modulated by Endogenous Action Potential Duration Gradients Rather Than Electrical Coupling in Ventricular Myocardium.Journal of the American Heart Association · 2025Article
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- Exploring the Impact of BKInternational journal of molecular sciences · 2024Review
- Use of acoustic cardiography to assess left ventricular electromechanical synchronization during left bundle branch pacing.Heart rhythm O2 · 2023Article
- Activation of small conductance CaThe Journal of physiology · 2023Article
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- Effective termination of atrial fibrillation by SK channel inhibition is associated with a sudden organization of fibrillatory conduction.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 · 2021Article
- The regulation of the small-conductance calcium-activated potassium current and the mechanisms of sex dimorphism in J wave syndrome.Pflugers Archiv : European journal of physiology · 2021Review
- Arrhythmogenic Mechanisms in Hypokalaemia: Insights From Pre-clinical Models.Frontiers in cardiovascular medicine · 2021Review
- Inhibition of Small-Conductance, CaFrontiers in pharmacology · 2021Article
- Proinflammatory Cytokine Modulates Intracellular Calcium Handling and Enhances Ventricular Arrhythmia Susceptibility.Frontiers in cardiovascular medicine · 2021Article
- Different arrhythmia-associated calmodulin mutations have distinct effects on cardiac SK channel regulation.The Journal of general physiology · 2020Article
- Hypokalemia Promotes Arrhythmia by Distinct Mechanisms in Atrial and Ventricular Myocytes.Circulation research · 2020Article
- Review
- Effects of ondansetron on apamin-sensitive small conductance calcium-activated potassium currents in pacing-induced failing rabbit hearts.Heart rhythm · 2020Article
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Authors and funding
10 authors at 7 institutions in 4 countries.
Yi-Hsin ChanFrom Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine (Y.-H.C., W.-C.T., P.-C.C., T.H.E., S.-F.L., P.-S.C.) and Wells Center for Pediatrics Research, Department of Pediatrics (M.R.), Indiana University School of Medicine, Indianapolis; Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taoyuan, Taiwan (Y.-H.C., P.-C.C.); Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung University College of Medicine, Taiwan (W.-C.T.); Division of Cardiology, Department of Internal Medicine, Wonkwang University School of Medicine and Hospital, Jeonbuk, Republic of Korea (J.-S.K.); Department of Cardiology, First Affiliated Hospital of Harbin Medical University, China (D.Y.); Departments of Medicine (Cardiology) and Physiology, University of California, Los Angeles (J.N.W.); and Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (S.-F.L.).
Wei-Chung TsaiFrom Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine (Y.-H.C., W.-C.T., P.-C.C., T.H.E., S.-F.L., P.-S.C.) and Wells Center for Pediatrics Research, Department of Pediatrics (M.R.), Indiana University School of Medicine, Indianapolis; Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taoyuan, Taiwan (Y.-H.C., P.-C.C.); Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung University College of Medicine, Taiwan (W.-C.T.); Division of Cardiology, Department of Internal Medicine, Wonkwang University School of Medicine and Hospital, Jeonbuk, Republic of Korea (J.-S.K.); Department of Cardiology, First Affiliated Hospital of Harbin Medical University, China (D.Y.); Departments of Medicine (Cardiology) and Physiology, University of California, Los Angeles (J.N.W.); and Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (S.-F.L.).
Jum-Suk KoFrom Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine (Y.-H.C., W.-C.T., P.-C.C., T.H.E., S.-F.L., P.-S.C.) and Wells Center for Pediatrics Research, Department of Pediatrics (M.R.), Indiana University School of Medicine, Indianapolis; Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taoyuan, Taiwan (Y.-H.C., P.-C.C.); Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung University College of Medicine, Taiwan (W.-C.T.); Division of Cardiology, Department of Internal Medicine, Wonkwang University School of Medicine and Hospital, Jeonbuk, Republic of Korea (J.-S.K.); Department of Cardiology, First Affiliated Hospital of Harbin Medical University, China (D.Y.); Departments of Medicine (Cardiology) and Physiology, University of California, Los Angeles (J.N.W.); and Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (S.-F.L.).
Dechun YinFrom Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine (Y.-H.C., W.-C.T., P.-C.C., T.H.E., S.-F.L., P.-S.C.) and Wells Center for Pediatrics Research, Department of Pediatrics (M.R.), Indiana University School of Medicine, Indianapolis; Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taoyuan, Taiwan (Y.-H.C., P.-C.C.); Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung University College of Medicine, Taiwan (W.-C.T.); Division of Cardiology, Department of Internal Medicine, Wonkwang University School of Medicine and Hospital, Jeonbuk, Republic of Korea (J.-S.K.); Department of Cardiology, First Affiliated Hospital of Harbin Medical University, China (D.Y.); Departments of Medicine (Cardiology) and Physiology, University of California, Los Angeles (J.N.W.); and Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (S.-F.L.).
Po-Cheng ChangFrom Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine (Y.-H.C., W.-C.T., P.-C.C., T.H.E., S.-F.L., P.-S.C.) and Wells Center for Pediatrics Research, Department of Pediatrics (M.R.), Indiana University School of Medicine, Indianapolis; Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taoyuan, Taiwan (Y.-H.C., P.-C.C.); Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung University College of Medicine, Taiwan (W.-C.T.); Division of Cardiology, Department of Internal Medicine, Wonkwang University School of Medicine and Hospital, Jeonbuk, Republic of Korea (J.-S.K.); Department of Cardiology, First Affiliated Hospital of Harbin Medical University, China (D.Y.); Departments of Medicine (Cardiology) and Physiology, University of California, Los Angeles (J.N.W.); and Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (S.-F.L.).
Michael RubartFrom Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine (Y.-H.C., W.-C.T., P.-C.C., T.H.E., S.-F.L., P.-S.C.) and Wells Center for Pediatrics Research, Department of Pediatrics (M.R.), Indiana University School of Medicine, Indianapolis; Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taoyuan, Taiwan (Y.-H.C., P.-C.C.); Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung University College of Medicine, Taiwan (W.-C.T.); Division of Cardiology, Department of Internal Medicine, Wonkwang University School of Medicine and Hospital, Jeonbuk, Republic of Korea (J.-S.K.); Department of Cardiology, First Affiliated Hospital of Harbin Medical University, China (D.Y.); Departments of Medicine (Cardiology) and Physiology, University of California, Los Angeles (J.N.W.); and Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (S.-F.L.).
James N WeissFrom Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine (Y.-H.C., W.-C.T., P.-C.C., T.H.E., S.-F.L., P.-S.C.) and Wells Center for Pediatrics Research, Department of Pediatrics (M.R.), Indiana University School of Medicine, Indianapolis; Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taoyuan, Taiwan (Y.-H.C., P.-C.C.); Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung University College of Medicine, Taiwan (W.-C.T.); Division of Cardiology, Department of Internal Medicine, Wonkwang University School of Medicine and Hospital, Jeonbuk, Republic of Korea (J.-S.K.); Department of Cardiology, First Affiliated Hospital of Harbin Medical University, China (D.Y.); Departments of Medicine (Cardiology) and Physiology, University of California, Los Angeles (J.N.W.); and Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (S.-F.L.).
Thomas H EverettFrom Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine (Y.-H.C., W.-C.T., P.-C.C., T.H.E., S.-F.L., P.-S.C.) and Wells Center for Pediatrics Research, Department of Pediatrics (M.R.), Indiana University School of Medicine, Indianapolis; Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taoyuan, Taiwan (Y.-H.C., P.-C.C.); Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung University College of Medicine, Taiwan (W.-C.T.); Division of Cardiology, Department of Internal Medicine, Wonkwang University School of Medicine and Hospital, Jeonbuk, Republic of Korea (J.-S.K.); Department of Cardiology, First Affiliated Hospital of Harbin Medical University, China (D.Y.); Departments of Medicine (Cardiology) and Physiology, University of California, Los Angeles (J.N.W.); and Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (S.-F.L.).
Shien-Fong LinFrom Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine (Y.-H.C., W.-C.T., P.-C.C., T.H.E., S.-F.L., P.-S.C.) and Wells Center for Pediatrics Research, Department of Pediatrics (M.R.), Indiana University School of Medicine, Indianapolis; Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taoyuan, Taiwan (Y.-H.C., P.-C.C.); Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung University College of Medicine, Taiwan (W.-C.T.); Division of Cardiology, Department of Internal Medicine, Wonkwang University School of Medicine and Hospital, Jeonbuk, Republic of Korea (J.-S.K.); Department of Cardiology, First Affiliated Hospital of Harbin Medical University, China (D.Y.); Departments of Medicine (Cardiology) and Physiology, University of California, Los Angeles (J.N.W.); and Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (S.-F.L.).
Peng-Sheng ChenFrom Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine (Y.-H.C., W.-C.T., P.-C.C., T.H.E., S.-F.L., P.-S.C.) and Wells Center for Pediatrics Research, Department of Pediatrics (M.R.), Indiana University School of Medicine, Indianapolis; Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taoyuan, Taiwan (Y.-H.C., P.-C.C.); Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung University College of Medicine, Taiwan (W.-C.T.); Division of Cardiology, Department of Internal Medicine, Wonkwang University School of Medicine and Hospital, Jeonbuk, Republic of Korea (J.-S.K.); Department of Cardiology, First Affiliated Hospital of Harbin Medical University, China (D.Y.); Departments of Medicine (Cardiology) and Physiology, University of California, Los Angeles (J.N.W.); and Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (S.-F.L.). chenpp@iu.edu.
University of California, Los Angeles · USFirst Affiliated Hospital of Harbin Medical University · CNChang Gung University · TWKaohsiung Medical University · TWLinkou Chang Gung Memorial Hospital · TWNational Yang Ming Chiao Tung University · TWWonkwang University · KR
Funding
Quality Assurance and Quality Control Project Management: Improving Submissions and Study Conduct in the Human Subjects Research Prior Approval ProcessUL1TR002529 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI MOE, SHARON M, WIEHE, SARAH ELIZABETH · 2018 to 2022
$27.2MIndiana Clinical and Translational Sciences InstituteUL1TR001108 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI DENNE, SCOTT C., SHEKHAR, ANANTHA · 2013 to 2017
$23.3MWAVE DYNAMICS IN NORMAL AND DISEASED RABBIT HEARTSP01HL078931 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WEISS, JAMES · 2005 to 2015
$20.7MThoracic Veins and Sustained Atrial FibrillationR01HL071140 · NHLBI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI CHEN, PENG-SHENG · 2002 to 2014
$4.7MSympathetic Nerve Activity Recorded From the Skin and Cardiac ArrhythmiasR41HL124741 · NHLBI · ARRHYTHMOTECH, LLC · PI EVERETT, THOMAS H · 2014 to 2014
$213kNCATS NIH HHS UL1 TR001108NHLBI NIH HHS P01 HL078931NHLBI NIH HHS P01 HL78931NHLBI NIH HHS R01 HL071140NHLBI NIH HHS R01 HL71140NHLBI NIH HHS R41 HL124741NHLBI NIH HHS R41HL124741
Abstract
backgroundHypokalemia increases the vulnerability to ventricular fibrillation. We hypothesize that the apamin-sensitive small-conductance calcium-activated potassium current (IKAS) is activated during hypokalemia and that IKAS blockade is proarrhythmic. METHODS AND
resultsOptical mapping was performed in 23 Langendorff-perfused rabbit ventricles with atrioventricular block and either right or left ventricular pacing during normokalemia or hypokalemia. Apamin prolonged the action potential duration (APD) measured to 80% repolarization (APD80) by 26 milliseconds (95% confidence interval [CI], 14-37) during normokalemia and by 54 milliseconds (95% CI, 40-68) during hypokalemia (P=0.01) at a 1000-millisecond pacing cycle length. In hypokalemic ventricles, apamin increased the maximal slope of APD restitution, the pacing cycle length threshold of APD alternans, the pacing cycle length for wave-break induction, and the area of spatially discordant APD alternans. Apamin significantly facilitated the induction of sustained ventricular fibrillation (from 3 of 9 hearts to 9 of 9 hearts; P=0.009). Short-term cardiac memory was assessed by the slope of APD80 versus activation time. The slope increased from 0.01 (95% CI, -0.09 to 0.12) at baseline to 0.34 (95% CI, 0.23-0.44) after apamin (P<0.001) during right ventricular pacing and from 0.07 (95% CI, -0.05 to 0.20) to 0.54 (95% CI, 0.06-1.03) after apamin infusion (P=0.045) during left ventricular pacing. Patch-clamp studies confirmed increased IKAS in isolated rabbit ventricular myocytes during hypokalemia (P=0.038).
conclusionsHypokalemia activates IKAS to shorten APD and maintain repolarization reserve at late activation sites during ventricular pacing. IKAS blockade prominently lengthens the APD at late activation sites and facilitates ventricular fibrillation induction.
Indexed as
Cardiac Pacing, ArtificialAction PotentialsAnimalsApaminDisease SusceptibilityHeart Conduction SystemHeart VentriclesHypokalemiaIntermediate-Conductance Calcium-Activated Potassium ChannelsMyocytes, CardiacPatch-Clamp TechniquesPotassiumPotassium Channel BlockersRabbitsVentricular FibrillationVoltage-Sensitive Dye ImagingApaminIntermediate-Conductance Calcium-Activated Potassium ChannelsPotassiumPotassium Channel Blockersarrhythmiascardiacdeathion channelssudden
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