{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T22:24:42Z","timestamp":1793658282365,"version":"4.5.1"},"reference-count":65,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2011,10,14]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              Understanding atrial fibrillation (AF) requires integrated understanding of ionic currents and Ca\n              <jats:sup>2+<\/jats:sup>\n              transport in remodeled human atrium, but appropriate models are limited.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>To study AF, we developed a new human atrial action potential (AP) model, derived from atrial experimental results and our human ventricular myocyte model.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              Atria versus ventricles have lower I\n              <jats:sub>K1<\/jats:sub>\n              , resulting in more depolarized resting membrane potential (\u22487 mV). We used higher I\n              <jats:sub>to,fast<\/jats:sub>\n              density in atrium, removed I\n              <jats:sub>to,slow<\/jats:sub>\n              , and included an atrial-specific I\n              <jats:sub>Kur<\/jats:sub>\n              . I\n              <jats:sub>NCX<\/jats:sub>\n              and I\n              <jats:sub>NaK<\/jats:sub>\n              densities were reduced in atrial versus ventricular myocytes according to experimental results. SERCA function was altered to reproduce human atrial myocyte Ca\n              <jats:sup>2+<\/jats:sup>\n              transients. To simulate chronic AF, we reduced I\n              <jats:sub>CaL<\/jats:sub>\n              , I\n              <jats:sub>to<\/jats:sub>\n              , I\n              <jats:sub>Kur<\/jats:sub>\n              and SERCA, and increased I\n              <jats:sub>K1<\/jats:sub>\n              ,I\n              <jats:sub>Ks<\/jats:sub>\n              and I\n              <jats:sub>NCX<\/jats:sub>\n              . We also investigated the link between Kv1.5 channelopathy, [Ca\n              <jats:sup>2+<\/jats:sup>\n              ]\n              <jats:sub>i<\/jats:sub>\n              , and AF. The sinus rhythm model showed a typical human atrial AP morphology. Consistent with experiments, the model showed shorter APs and reduced AP duration shortening at increasing pacing frequencies in AF or when I\n              <jats:sub>CaL<\/jats:sub>\n              was partially blocked, suggesting a crucial role of Ca\n              <jats:sup>2+<\/jats:sup>\n              and Na\n              <jats:sup>+<\/jats:sup>\n              in this effect. This also explained blunted Ca\n              <jats:sup>2+<\/jats:sup>\n              transient and rate-adaptation of [Ca\n              <jats:sup>2+<\/jats:sup>\n              ]\n              <jats:sub>i<\/jats:sub>\n              and [Na\n              <jats:sup>+<\/jats:sup>\n              ]\n              <jats:sub>i<\/jats:sub>\n              in chronic AF. Moreover, increasing [Na\n              <jats:sup>+<\/jats:sup>\n              ]\n              <jats:sub>i<\/jats:sub>\n              and altered I\n              <jats:sub>NaK<\/jats:sub>\n              and I\n              <jats:sub>NCX<\/jats:sub>\n              causes rate-dependent atrial AP shortening. Blocking I\n              <jats:sub>Kur<\/jats:sub>\n              to mimic Kv1.5 loss-of-function increased [Ca\n              <jats:sup>2+<\/jats:sup>\n              ]\n              <jats:sub>i<\/jats:sub>\n              and caused early afterdepolarizations under adrenergic stress, as observed experimentally.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              Our study provides a novel tool and insights into ionic bases of atrioventricular AP differences, and shows how Na\n              <jats:sup>+<\/jats:sup>\n              and Ca\n              <jats:sup>2+<\/jats:sup>\n              homeostases critically mediate abnormal repolarization in AF.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.111.253955","type":"journal-article","created":{"date-parts":[[2011,9,16]],"date-time":"2011-09-16T11:09:12Z","timestamp":1316171352000},"page":"1055-1066","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":350,"title":["Human Atrial Action Potential and Ca\n            <sup>2+<\/sup>\n            Model"],"prefix":"10.1161","volume":"109","author":[{"given":"Eleonora","family":"Grandi","sequence":"first","affiliation":[{"name":"From the Department of Pharmacology, University of California, Davis, Davis, CA (E.G., D.M.B.); Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI (S.V.P., J.J.); the Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., D.D.); and the Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.J.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep V.","family":"Pandit","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, University of California, Davis, Davis, CA (E.G., D.M.B.); Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI (S.V.P., J.J.); the Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., D.D.); and the Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.J.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Voigt","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, University of California, Davis, Davis, CA (E.G., D.M.B.); Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI (S.V.P., J.J.); the Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., D.D.); and the Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.J.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antony J.","family":"Workman","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, University of California, Davis, Davis, CA (E.G., D.M.B.); Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI (S.V.P., J.J.); the Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., D.D.); and the Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.J.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dobromir","family":"Dobrev","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, University of California, Davis, Davis, CA (E.G., D.M.B.); Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI (S.V.P., J.J.); the Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., D.D.); and the Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.J.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Jalife","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, University of California, Davis, Davis, CA (E.G., D.M.B.); Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI (S.V.P., J.J.); the Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., D.D.); and the Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.J.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald M.","family":"Bers","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, University of California, Davis, Davis, CA (E.G., D.M.B.); Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI (S.V.P., J.J.); the Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., D.D.); and the Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom 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Fibrillation"],"short-title":[],"issued":{"date-parts":[[2011,10,14]]},"references-count":65,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2011,10,14]]}},"alternative-id":["10.1161\/CIRCRESAHA.111.253955"],"URL":"https:\/\/doi.org\/10.1161\/circresaha.111.253955","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,10,14]]},"assertion":[{"value":"2011-08-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-08-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-09-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}