{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:44:30Z","timestamp":1791121470246,"version":"4.1.0"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"24","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2005,12,13]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic>Background\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    The molecular mechanism of increased background inward rectifier current (\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>K1<\/jats:sub>\n                    ) in atrial fibrillation (AF) is not fully understood. We tested whether constitutively active acetylcholine (ACh)-activated\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>K,ACh<\/jats:sub>\n                    contributes to enhanced basal conductance in chronic AF (cAF).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Methods and Results\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    Whole-cell and single-channel currents were measured with standard voltage-clamp techniques in atrial myocytes from patients with sinus rhythm (SR) and cAF. The selective\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>K,ACh<\/jats:sub>\n                    blocker tertiapin was used for inhibition of\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>K,ACh<\/jats:sub>\n                    . Whole-cell basal current was larger in cAF than in SR, whereas carbachol (CCh)-activated\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>K,ACh<\/jats:sub>\n                    was lower in cAF than in SR. Tertiapin (0.1 to 100 nmol\/L) reduced\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>K,ACh<\/jats:sub>\n                    in a concentration-dependent manner with greater potency in cAF than in SR (\u2212logIC\n                    <jats:sub>50<\/jats:sub>\n                    : 9.1 versus 8.2;\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05). Basal current contained a tertiapin-sensitive component that was larger in cAF than in SR (tertiapin [10 nmol\/L]-sensitive current at \u2212100 mV: cAF, \u22126.7\u00b11.2 pA\/pF, n=16\/5 [myocytes\/patients] versus SR, \u22121.7\u00b10.5 pA\/pF, n=24\/8), suggesting contribution of constitutively active\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>K,ACh<\/jats:sub>\n                    to basal current. In single-channel recordings, constitutively active\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>K,ACh<\/jats:sub>\n                    was prominent in cAF but not in SR (channel open probability: cAF, 5.4\u00b10.7%, n=19\/9 versus SR, 0.1\u00b10.05%, n=16\/9;\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05). Moreover,\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>K1<\/jats:sub>\n                    channel open probability was higher in cAF than in SR (13.4\u00b10.4%, n=19\/9 versus 11.4\u00b10.7%, n=16\/9;\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05) without changes in other channel characteristics.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Conclusions\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    Our results demonstrate that larger basal inward rectifier K\n                    <jats:sup>+<\/jats:sup>\n                    current in cAF consists of increased\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>K1<\/jats:sub>\n                    activity and constitutively active\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>K,ACh<\/jats:sub>\n                    . Blockade of\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>K,ACh<\/jats:sub>\n                    may represent a new therapeutic target in AF.\n                  <\/jats:p>","DOI":"10.1161\/circulationaha.105.575332","type":"journal-article","created":{"date-parts":[[2005,12,5]],"date-time":"2005-12-05T20:34:53Z","timestamp":1133814893000},"page":"3697-3706","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":413,"title":["The G Protein\u2013Gated Potassium Current\n                    <i>I<\/i>\n                    <sub>K,ACh<\/sub>\n                    Is Constitutively Active in Patients With Chronic Atrial Fibrillation"],"prefix":"10.1161","volume":"112","author":[{"given":"D.","family":"Dobrev","sequence":"first","affiliation":[{"name":"From the Department of Pharmacology and Toxicology (D.D., A.F., N.V., E.W., T.C., U.R.) and Cardiovascular Center (M.K.), Medical Faculty, Dresden University of Technology, Dresden, Germany; and Department of Pharmacology and Pharmacotherapy (N.J.), Medical University of Szeged, Szeged, Hungary."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Friedrich","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Toxicology (D.D., A.F., N.V., E.W., T.C., U.R.) and Cardiovascular Center (M.K.), Medical Faculty, Dresden University of Technology, Dresden, Germany; and Department of Pharmacology and Pharmacotherapy (N.J.), Medical University of Szeged, Szeged, Hungary."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Voigt","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Toxicology (D.D., A.F., N.V., E.W., T.C., U.R.) and Cardiovascular Center (M.K.), Medical Faculty, Dresden University of Technology, Dresden, Germany; and Department of Pharmacology and Pharmacotherapy (N.J.), Medical University of Szeged, Szeged, Hungary."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Jost","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Toxicology (D.D., A.F., N.V., E.W., T.C., U.R.) and Cardiovascular Center (M.K.), Medical Faculty, Dresden University of Technology, Dresden, Germany; and Department of Pharmacology and Pharmacotherapy (N.J.), Medical University of Szeged, Szeged, Hungary."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Wettwer","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Toxicology (D.D., A.F., N.V., E.W., T.C., U.R.) and Cardiovascular Center (M.K.), Medical Faculty, Dresden University of Technology, Dresden, Germany; and Department of Pharmacology and Pharmacotherapy (N.J.), Medical University of Szeged, Szeged, Hungary."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Christ","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Toxicology (D.D., A.F., N.V., E.W., T.C., U.R.) and Cardiovascular Center (M.K.), Medical Faculty, Dresden University of Technology, Dresden, Germany; and Department of Pharmacology and Pharmacotherapy (N.J.), Medical University of Szeged, Szeged, Hungary."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Knaut","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Toxicology (D.D., A.F., N.V., E.W., T.C., U.R.) and Cardiovascular Center (M.K.), Medical Faculty, Dresden University of Technology, Dresden, Germany; and Department of Pharmacology and Pharmacotherapy (N.J.), Medical University of Szeged, Szeged, Hungary."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U.","family":"Ravens","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Toxicology (D.D., A.F., N.V., E.W., T.C., U.R.) and Cardiovascular Center (M.K.), Medical Faculty, Dresden University of Technology, Dresden, Germany; and Department of Pharmacology and Pharmacotherapy (N.J.), Medical University of Szeged, Szeged, Hungary."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/415219a"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-003-0409-8"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.80.6.772"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(99)00178-9"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.85.5.428"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.104.21.2551"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(01)00555-7"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000145659.80212.6a"},{"key":"e_1_3_2_9_2","first-page":"H805","volume":"273","year":"1997","unstructured":"Liu L, Nattel S. 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