{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:21:56Z","timestamp":1790767316225,"version":"4.1.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2015,7,14]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>\n              Antiarrhythmic management of atrial fibrillation (AF) remains a major clinical challenge. Mechanism-based approaches to AF therapy are sought to increase effectiveness and to provide individualized patient care. K\n              <jats:sub>2P<\/jats:sub>\n              3.1 (TASK-1 [tandem of P domains in a weak inward-rectifying K\n              <jats:sup>+<\/jats:sup>\n              channel\u2013related acid-sensitive K\n              <jats:sup>+<\/jats:sup>\n              channel-1]) 2-pore-domain K\n              <jats:sup>+<\/jats:sup>\n              (K\n              <jats:sub>2P<\/jats:sub>\n              ) channels have been implicated in action potential regulation in animal models. However, their role in the pathophysiology and treatment of paroxysmal and chronic patients with AF is unknown.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              Right and left atrial tissue was obtained from patients with paroxysmal or chronic AF and from control subjects in sinus rhythm. Ion channel expression was analyzed by quantitative real-time polymerase chain reaction and Western blot. Membrane currents and action potentials were recorded using voltage- and current-clamp techniques. K\n              <jats:sub>2P<\/jats:sub>\n              3.1 subunits exhibited predominantly atrial expression, and atrial K\n              <jats:sub>2P<\/jats:sub>\n              3.1 transcript levels were highest among functional K\n              <jats:sub>2P<\/jats:sub>\n              channels. K\n              <jats:sub>2P<\/jats:sub>\n              3.1 mRNA and protein levels were increased in chronic AF. Enhancement of corresponding currents in the right atrium resulted in shortened action potential duration at 90% of repolarization (APD\n              <jats:sub>90<\/jats:sub>\n              ) compared with patients in sinus rhythm. In contrast, K\n              <jats:sub>2P<\/jats:sub>\n              3.1 expression was not significantly affected in subjects with paroxysmal AF. Pharmacological K\n              <jats:sub>2P<\/jats:sub>\n              3.1 inhibition prolonged APD\n              <jats:sub>90<\/jats:sub>\n              in atrial myocytes from patients with chronic AF to values observed among control subjects in sinus rhythm.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>\n              Enhancement of atrium-selective K\n              <jats:sub>2P<\/jats:sub>\n              3.1 currents contributes to APD shortening in patients with chronic AF, and K\n              <jats:sub>2P<\/jats:sub>\n              3.1 channel inhibition reverses AF-related APD shortening. These results highlight the potential of K\n              <jats:sub>2P<\/jats:sub>\n              3.1 as a novel drug target for mechanism-based AF therapy.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.114.012657","type":"journal-article","created":{"date-parts":[[2015,5,8]],"date-time":"2015-05-08T03:12:01Z","timestamp":1431054721000},"page":"82-92","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":203,"title":["Upregulation of K\n            <sub>2P<\/sub>\n            3.1 K\n            <sup>+<\/sup>\n            Current Causes Action Potential Shortening in Patients With Chronic Atrial Fibrillation"],"prefix":"10.1161","volume":"132","author":[{"given":"Constanze","family":"Schmidt","sequence":"first","affiliation":[{"name":"From Department of Cardiology, University of Heidelberg, Germany (C.S., F.W., V.A., P.L., P.A.S., H.A.K., D.T.); Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., X.-B.Z., J.H., S.L., M.B., D.D.); Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany (N.V., J.H., D.D.); First Department of Medicine, University Medical Center Mannheim, Germany (X.-B.Z., S.L., M.B.); Department for Bioinformatics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Wiedmann","sequence":"additional","affiliation":[{"name":"From Department of Cardiology, University of Heidelberg, Germany (C.S., F.W., V.A., P.L., P.A.S., H.A.K., D.T.); Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., X.-B.Z., J.H., S.L., M.B., D.D.); Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany (N.V., J.H., D.D.); First Department of Medicine, University Medical Center Mannheim, Germany (X.-B.Z., S.L., M.B.); Department for Bioinformatics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Voigt","sequence":"additional","affiliation":[{"name":"From Department of Cardiology, University of Heidelberg, Germany (C.S., F.W., V.A., P.L., P.A.S., H.A.K., D.T.); Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., X.-B.Z., J.H., S.L., M.B., D.D.); Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany (N.V., J.H., D.D.); First Department of Medicine, University Medical Center Mannheim, Germany (X.-B.Z., S.L., M.B.); Department for Bioinformatics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Bo","family":"Zhou","sequence":"additional","affiliation":[{"name":"From Department of Cardiology, University of Heidelberg, Germany (C.S., F.W., V.A., P.L., P.A.S., H.A.K., D.T.); Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., X.-B.Z., J.H., S.L., M.B., D.D.); Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany (N.V., J.H., D.D.); First Department of Medicine, University Medical Center Mannheim, Germany (X.-B.Z., S.L., M.B.); Department for Bioinformatics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Heijman","sequence":"additional","affiliation":[{"name":"From Department of Cardiology, University of Heidelberg, Germany (C.S., F.W., V.A., P.L., P.A.S., H.A.K., D.T.); Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., X.-B.Z., J.H., S.L., M.B., D.D.); Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany (N.V., J.H., D.D.); First Department of Medicine, University Medical Center Mannheim, Germany (X.-B.Z., S.L., M.B.); Department for Bioinformatics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siegfried","family":"Lang","sequence":"additional","affiliation":[{"name":"From Department of Cardiology, University of Heidelberg, Germany (C.S., F.W., V.A., P.L., P.A.S., H.A.K., D.T.); Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., X.-B.Z., J.H., S.L., M.B., D.D.); Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany (N.V., J.H., D.D.); First Department of Medicine, University Medical Center Mannheim, Germany (X.-B.Z., S.L., M.B.); Department for Bioinformatics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Albert","sequence":"additional","affiliation":[{"name":"From Department of Cardiology, University of Heidelberg, Germany (C.S., F.W., V.A., P.L., P.A.S., H.A.K., D.T.); Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., X.-B.Z., J.H., S.L., M.B., D.D.); Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany (N.V., J.H., D.D.); First Department of Medicine, University Medical Center Mannheim, Germany (X.-B.Z., S.L., M.B.); Department for Bioinformatics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Kallenberger","sequence":"additional","affiliation":[{"name":"From Department of Cardiology, University of Heidelberg, Germany (C.S., F.W., V.A., P.L., P.A.S., H.A.K., D.T.); Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., X.-B.Z., J.H., S.L., M.B., D.D.); Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany (N.V., J.H., D.D.); First Department of Medicine, University Medical Center Mannheim, Germany (X.-B.Z., S.L., M.B.); Department for Bioinformatics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjang","family":"Ruhparwar","sequence":"additional","affiliation":[{"name":"From Department of Cardiology, University of Heidelberg, Germany (C.S., F.W., V.A., P.L., P.A.S., H.A.K., D.T.); Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., X.-B.Z., J.H., S.L., M.B., D.D.); Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany (N.V., J.H., D.D.); First Department of Medicine, University Medical Center Mannheim, Germany (X.-B.Z., S.L., M.B.); Department for Bioinformatics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e1bor","family":"Szab\u00f3","sequence":"additional","affiliation":[{"name":"From Department of Cardiology, University of Heidelberg, Germany (C.S., F.W., V.A., P.L., P.A.S., H.A.K., D.T.); Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., X.-B.Z., J.H., S.L., M.B., D.D.); Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany (N.V., J.H., D.D.); First Department of Medicine, University Medical Center Mannheim, Germany (X.-B.Z., S.L., M.B.); Department for Bioinformatics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Kallenbach","sequence":"additional","affiliation":[{"name":"From Department of Cardiology, University of Heidelberg, Germany (C.S., F.W., V.A., P.L., P.A.S., H.A.K., D.T.); Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., X.-B.Z., J.H., S.L., M.B., D.D.); Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany (N.V., J.H., D.D.); First Department of Medicine, University Medical Center Mannheim, Germany (X.-B.Z., S.L., M.B.); Department for Bioinformatics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Karck","sequence":"additional","affiliation":[{"name":"From Department of Cardiology, University of Heidelberg, Germany (C.S., F.W., V.A., P.L., P.A.S., H.A.K., D.T.); Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., X.-B.Z., J.H., S.L., M.B., D.D.); Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany (N.V., J.H., D.D.); First Department of Medicine, University Medical Center Mannheim, Germany (X.-B.Z., S.L., M.B.); Department for Bioinformatics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Borggrefe","sequence":"additional","affiliation":[{"name":"From Department of Cardiology, University of Heidelberg, Germany (C.S., F.W., V.A., P.L., P.A.S., H.A.K., D.T.); Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., X.-B.Z., J.H., S.L., M.B., D.D.); Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany (N.V., J.H., D.D.); First Department of Medicine, University Medical Center Mannheim, Germany (X.-B.Z., S.L., M.B.); Department for Bioinformatics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Biliczki","sequence":"additional","affiliation":[{"name":"From Department of Cardiology, University of Heidelberg, Germany (C.S., F.W., V.A., P.L., P.A.S., H.A.K., D.T.); Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., X.-B.Z., J.H., S.L., M.B., D.D.); Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany (N.V., J.H., D.D.); First Department of Medicine, University Medical Center Mannheim, Germany (X.-B.Z., S.L., M.B.); Department for Bioinformatics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim R.","family":"Ehrlich","sequence":"additional","affiliation":[{"name":"From Department of Cardiology, University of Heidelberg, Germany (C.S., F.W., V.A., P.L., P.A.S., H.A.K., D.T.); Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., X.-B.Z., J.H., S.L., M.B., D.D.); Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany (N.V., J.H., D.D.); First Department of Medicine, University Medical Center Mannheim, Germany (X.-B.Z., S.L., M.B.); Department for Bioinformatics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Istv\u00e1n","family":"Baczk\u00f3","sequence":"additional","affiliation":[{"name":"From Department of Cardiology, University of Heidelberg, Germany (C.S., F.W., V.A., P.L., P.A.S., H.A.K., D.T.); Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., X.-B.Z., J.H., S.L., M.B., D.D.); Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany (N.V., J.H., D.D.); First Department of Medicine, University Medical Center Mannheim, Germany (X.-B.Z., S.L., M.B.); Department for Bioinformatics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Lugenbiel","sequence":"additional","affiliation":[{"name":"From Department of Cardiology, University of Heidelberg, Germany (C.S., F.W., V.A., P.L., P.A.S., H.A.K., D.T.); Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., X.-B.Z., J.H., S.L., M.B., D.D.); Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany (N.V., J.H., D.D.); First Department of Medicine, University Medical Center Mannheim, Germany (X.-B.Z., S.L., M.B.); Department for Bioinformatics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick A.","family":"Schweizer","sequence":"additional","affiliation":[{"name":"From Department of Cardiology, University of Heidelberg, Germany (C.S., F.W., V.A., P.L., P.A.S., H.A.K., D.T.); Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., X.-B.Z., J.H., S.L., M.B., D.D.); Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany (N.V., J.H., D.D.); First Department of Medicine, University Medical Center Mannheim, Germany (X.-B.Z., S.L., M.B.); Department for Bioinformatics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit C.","family":"Donner","sequence":"additional","affiliation":[{"name":"From Department of Cardiology, University of Heidelberg, Germany (C.S., F.W., V.A., P.L., P.A.S., H.A.K., D.T.); Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., X.-B.Z., J.H., S.L., M.B., D.D.); Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany (N.V., J.H., D.D.); First Department of Medicine, University Medical Center Mannheim, Germany (X.-B.Z., S.L., M.B.); Department for Bioinformatics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo A.","family":"Katus","sequence":"additional","affiliation":[{"name":"From Department of Cardiology, University of Heidelberg, Germany (C.S., F.W., V.A., P.L., P.A.S., H.A.K., D.T.); Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., X.-B.Z., J.H., S.L., M.B., D.D.); Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany (N.V., J.H., D.D.); First Department of Medicine, University Medical Center Mannheim, Germany (X.-B.Z., S.L., M.B.); Department for Bioinformatics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dobromir","family":"Dobrev","sequence":"additional","affiliation":[{"name":"From Department of Cardiology, University of Heidelberg, Germany (C.S., F.W., V.A., P.L., P.A.S., H.A.K., D.T.); Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., X.-B.Z., J.H., S.L., M.B., D.D.); Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany (N.V., J.H., D.D.); First Department of Medicine, University Medical Center Mannheim, Germany (X.-B.Z., S.L., M.B.); 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