ArticleCirculation. Arrhythmia and electrophysiology2015
Small conductance calcium-activated potassium current is important in transmural repolarization of failing human ventricles.
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Article in Circulation. Arrhythmia and electrophysiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 33 citations in OpenAlex.
- Local calcium dynamics and signalling in cardiomyocytes.Nature reviews. Cardiology · 2026Review
- BACH2 links β1-adrenergic receptor/β-arrestin1 signaling to MIAT to inhibit cardiac fibroblast activation and cardiomyocyte apoptosis.Cell death discovery · 2026Article
- Antiarrhythmic effects of mirabegron on ventricular fibrillation in Langendorff-perfused rabbit ventricles.The Journal of physiology · 2025Article
- Small-conductance calcium-activated potassium channels in the heart: expression, regulation and pathological implications.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- MiR-150 Attenuates Maladaptive Cardiac Remodeling Mediated by Long Noncoding RNA MIAT and Directly Represses ProfibroticCirculation. Heart failure · 2022Article
- Cardiomyocyte microRNA-150 confers cardiac protection and directly represses proapoptotic small proline-rich protein 1A.JCI insight · 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
- Sex-specific IHeart rhythm · 2021Article
- Review
- Concomitant SK current activation and sodium current inhibition cause J wave syndrome.JCI insight · 2018Article
- Sex-specific activation of SK current by isoproterenol facilitates action potential triangulation and arrhythmogenesis in rabbit ventricles.The Journal of physiology · 2018Article
- Role of apamin-sensitive small conductance calcium-activated potassium currents in long-term cardiac memory in rabbits.Heart rhythm · 2018Article
- Complex electrophysiological remodeling in postinfarction ischemic heart failure.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Small-Conductance Calcium-Activated Potassium Current in Normal Rabbit Cardiac Purkinje Cells.Journal of the American Heart Association · 2017Article
- Dynamical effects of calcium-sensitive potassium currents on voltage and calcium alternans.The Journal of physiology · 2017Article
- Role of Apamin-Sensitive Calcium-Activated Small-Conductance Potassium Currents on the Mechanisms of Ventricular Fibrillation in Pacing-Induced Failing Rabbit Hearts.Circulation. Arrhythmia and electrophysiology · 2017Article
- Murine Electrophysiological Models of Cardiac Arrhythmogenesis.Physiological reviews · 2017Review
- Antiarrhythmic effect of the CaPflugers Archiv : European journal of physiology · 2016Article
- KCNN2 polymorphisms and cardiac tachyarrhythmias.Medicine · 2016Article
- Arrhythmia Protection in Hypokalemia: A Novel Role of Ca2+-Activated K+ Currents in the Ventricle.Circulation · 2015Article
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Authors and funding
12 authors at 5 institutions in 2 countries.
Chih-Chieh YuFrom the Department of Medicine, Division of Cardiology, Krannert Institute of Cardiology (C.-C.Y., C.C., R.S., M.Y., I.B.R., S.S., Z.C., S.-F.L., J.C.L., P.-S.C.) and Department of Biostatistics (C.S.), Indiana University School of Medicine, Indianapolis; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (C.-C.Y.); Fairbanks School of Public Health, School of Medicine, Indiana University, Indianapolis (C.S.); Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles (M.C.F.); Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (S.-F.L.); and Department of Medicine, Roudebush Veterans Affairs Medical Center, Indianapolis, IN (J.C.L.).
Christopher CorrFrom the Department of Medicine, Division of Cardiology, Krannert Institute of Cardiology (C.-C.Y., C.C., R.S., M.Y., I.B.R., S.S., Z.C., S.-F.L., J.C.L., P.-S.C.) and Department of Biostatistics (C.S.), Indiana University School of Medicine, Indianapolis; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (C.-C.Y.); Fairbanks School of Public Health, School of Medicine, Indiana University, Indianapolis (C.S.); Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles (M.C.F.); Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (S.-F.L.); and Department of Medicine, Roudebush Veterans Affairs Medical Center, Indianapolis, IN (J.C.L.).
Changyu ShenFrom the Department of Medicine, Division of Cardiology, Krannert Institute of Cardiology (C.-C.Y., C.C., R.S., M.Y., I.B.R., S.S., Z.C., S.-F.L., J.C.L., P.-S.C.) and Department of Biostatistics (C.S.), Indiana University School of Medicine, Indianapolis; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (C.-C.Y.); Fairbanks School of Public Health, School of Medicine, Indiana University, Indianapolis (C.S.); Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles (M.C.F.); Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (S.-F.L.); and Department of Medicine, Roudebush Veterans Affairs Medical Center, Indianapolis, IN (J.C.L.).
Richard SheltonFrom the Department of Medicine, Division of Cardiology, Krannert Institute of Cardiology (C.-C.Y., C.C., R.S., M.Y., I.B.R., S.S., Z.C., S.-F.L., J.C.L., P.-S.C.) and Department of Biostatistics (C.S.), Indiana University School of Medicine, Indianapolis; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (C.-C.Y.); Fairbanks School of Public Health, School of Medicine, Indiana University, Indianapolis (C.S.); Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles (M.C.F.); Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (S.-F.L.); and Department of Medicine, Roudebush Veterans Affairs Medical Center, Indianapolis, IN (J.C.L.).
Mrinal YadavaFrom the Department of Medicine, Division of Cardiology, Krannert Institute of Cardiology (C.-C.Y., C.C., R.S., M.Y., I.B.R., S.S., Z.C., S.-F.L., J.C.L., P.-S.C.) and Department of Biostatistics (C.S.), Indiana University School of Medicine, Indianapolis; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (C.-C.Y.); Fairbanks School of Public Health, School of Medicine, Indiana University, Indianapolis (C.S.); Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles (M.C.F.); Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (S.-F.L.); and Department of Medicine, Roudebush Veterans Affairs Medical Center, Indianapolis, IN (J.C.L.).
Isaac B RheaFrom the Department of Medicine, Division of Cardiology, Krannert Institute of Cardiology (C.-C.Y., C.C., R.S., M.Y., I.B.R., S.S., Z.C., S.-F.L., J.C.L., P.-S.C.) and Department of Biostatistics (C.S.), Indiana University School of Medicine, Indianapolis; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (C.-C.Y.); Fairbanks School of Public Health, School of Medicine, Indiana University, Indianapolis (C.S.); Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles (M.C.F.); Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (S.-F.L.); and Department of Medicine, Roudebush Veterans Affairs Medical Center, Indianapolis, IN (J.C.L.).
Susan StrakaFrom the Department of Medicine, Division of Cardiology, Krannert Institute of Cardiology (C.-C.Y., C.C., R.S., M.Y., I.B.R., S.S., Z.C., S.-F.L., J.C.L., P.-S.C.) and Department of Biostatistics (C.S.), Indiana University School of Medicine, Indianapolis; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (C.-C.Y.); Fairbanks School of Public Health, School of Medicine, Indiana University, Indianapolis (C.S.); Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles (M.C.F.); Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (S.-F.L.); and Department of Medicine, Roudebush Veterans Affairs Medical Center, Indianapolis, IN (J.C.L.).
Michael C FishbeinFrom the Department of Medicine, Division of Cardiology, Krannert Institute of Cardiology (C.-C.Y., C.C., R.S., M.Y., I.B.R., S.S., Z.C., S.-F.L., J.C.L., P.-S.C.) and Department of Biostatistics (C.S.), Indiana University School of Medicine, Indianapolis; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (C.-C.Y.); Fairbanks School of Public Health, School of Medicine, Indiana University, Indianapolis (C.S.); Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles (M.C.F.); Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (S.-F.L.); and Department of Medicine, Roudebush Veterans Affairs Medical Center, Indianapolis, IN (J.C.L.).
Zhenhui ChenFrom the Department of Medicine, Division of Cardiology, Krannert Institute of Cardiology (C.-C.Y., C.C., R.S., M.Y., I.B.R., S.S., Z.C., S.-F.L., J.C.L., P.-S.C.) and Department of Biostatistics (C.S.), Indiana University School of Medicine, Indianapolis; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (C.-C.Y.); Fairbanks School of Public Health, School of Medicine, Indiana University, Indianapolis (C.S.); Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles (M.C.F.); Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (S.-F.L.); and Department of Medicine, Roudebush Veterans Affairs Medical Center, Indianapolis, IN (J.C.L.).
Shien-Fong LinFrom the Department of Medicine, Division of Cardiology, Krannert Institute of Cardiology (C.-C.Y., C.C., R.S., M.Y., I.B.R., S.S., Z.C., S.-F.L., J.C.L., P.-S.C.) and Department of Biostatistics (C.S.), Indiana University School of Medicine, Indianapolis; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (C.-C.Y.); Fairbanks School of Public Health, School of Medicine, Indiana University, Indianapolis (C.S.); Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles (M.C.F.); Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (S.-F.L.); and Department of Medicine, Roudebush Veterans Affairs Medical Center, Indianapolis, IN (J.C.L.).
John C LopshireFrom the Department of Medicine, Division of Cardiology, Krannert Institute of Cardiology (C.-C.Y., C.C., R.S., M.Y., I.B.R., S.S., Z.C., S.-F.L., J.C.L., P.-S.C.) and Department of Biostatistics (C.S.), Indiana University School of Medicine, Indianapolis; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (C.-C.Y.); Fairbanks School of Public Health, School of Medicine, Indiana University, Indianapolis (C.S.); Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles (M.C.F.); Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (S.-F.L.); and Department of Medicine, Roudebush Veterans Affairs Medical Center, Indianapolis, IN (J.C.L.).
Peng-Sheng ChenFrom the Department of Medicine, Division of Cardiology, Krannert Institute of Cardiology (C.-C.Y., C.C., R.S., M.Y., I.B.R., S.S., Z.C., S.-F.L., J.C.L., P.-S.C.) and Department of Biostatistics (C.S.), Indiana University School of Medicine, Indianapolis; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (C.-C.Y.); Fairbanks School of Public Health, School of Medicine, Indiana University, Indianapolis (C.S.); Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles (M.C.F.); Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (S.-F.L.); and Department of Medicine, Roudebush Veterans Affairs Medical Center, Indianapolis, IN (J.C.L.). chenpp@iu.edu.
National Taiwan University Hospital · TWIndiana University IndianapolisNational Yang Ming Chiao Tung University · TWIndiana University – Purdue University Indianapolis · USUniversity of California, Los Angeles · US
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 HL124741
Abstract
backgroundThe transmural distribution of apamin-sensitive small conductance Ca(2+)-activated K(+) (SK) current (IKAS) in failing human ventricles remains unclear. METHODS AND
resultsWe optically mapped left ventricular wedge preparations from 12 failing native hearts and 2 rejected cardiac allografts explanted during transplant surgery. We determined transmural action potential duration (APD) before and after 100 nmol/L apamin administration in all wedges and after sequential administration of apamin, chromanol, and E4031 in 4 wedges. Apamin prolonged APD from 363 ms (95% confidence interval [CI], 341-385) to 409 (95% CI, 385-434; P<0.001) in all hearts, and reduced the transmural conduction velocity from 36 cm/s (95% CI, 30-42) to 32 cm/s (95% CI, 27-37; P=0.001) in 12 native failing hearts at 1000 ms pacing cycle length (PCL). The percent APD prolongation is negatively correlated with baseline APD and positively correlated with PCL. Only 1 wedge had M-cell islands. The percentages of APD prolongation in the last 4 hearts at 2000 ms PCL after apamin, chromanol, and E4031 were 9.1% (95% CI, 3.9-14.2), 17.3% (95% CI, 3.1-31.5), and 35.9% (95% CI, 15.7-56.1), respectively. Immunohistochemical staining of subtype 2 of SK protein showed increased expression in intercalated discs of myocytes.
conclusionsSK current is important in the transmural repolarization in failing human ventricles. The magnitude of IKAS is positively correlated with the PCL, but negatively correlated with APD when PCL is fixed. There is abundant subtype 2 of SK protein in the intercalated discs of myocytes.
Indexed as
Action PotentialsAdultAgedCardiac Pacing, ArtificialFemaleHeart FailureHeart VentriclesHumansIn Vitro TechniquesMaleMiddle AgedPerfusionPotassiumPotassium Channel BlockersSmall-Conductance Calcium-Activated Potassium ChannelsStroke VolumeKCNN2 protein, humanPotassiumPotassium Channel BlockersSmall-Conductance Calcium-Activated Potassium Channelsaction potentialcalciumheart failureion channelsventricular remodeling
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