{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T23:20:31Z","timestamp":1791069631485,"version":"4.1.0"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[1997,12]]},"abstract":"<jats:p><jats:italic>Abstract<\/jats:italic>We have previously shown that chronic rapid atrial activation (400 bpm) reduces atrial conduction velocity in dogs, contributing to the development of a substrate supporting sustained atrial fibrillation (AF). However, the cellular and ionic mechanisms underlying these functional changes have not been defined. We applied whole-cell patch-clamp techniques to atrial myocytes from dogs subjected to atrial pacing at 400 bpm for 7 days (P7, n=6) and 42 days (P42, n=5) and compared the results with those from sham-operated dogs similarly instrumented but without pacemaker activation (P0, n=6). Rapid atrial pacing allowed for the induction of sustained AF in 67% and 100% of dogs paced for 7 and 42 days, respectively, and significantly decreased conduction velocity under P7 and P42 conditions. In dogs paced for 7 days, Na<jats:sup>+<\/jats:sup>current (<jats:italic>I<\/jats:italic><jats:sub>Na<\/jats:sub>) density was reduced by 28% at \u221240 mV (<jats:italic>P<\/jats:italic>&lt;.0001, n=59 cells).<jats:italic>I<\/jats:italic><jats:sub>Na<\/jats:sub>changes were even more decreased under P42 conditions, by \u224852% at \u221240 mV (<jats:italic>P<\/jats:italic>&lt;.0001): from \u221278.7\u00b14.6 pA\/pF (P0, n=28 cells) to \u221237.7\u00b13.0 pA\/pF (P42, n=43 cells).<jats:italic>I<\/jats:italic><jats:sub>Na<\/jats:sub>was significantly reduced at all voltages ranging from \u221265 to \u221210 mV. Voltage-dependent activation and inactivation properties, activation kinetics, and recovery from inactivation were not altered by rapid atrial pacing; however, inactivation kinetics were slowed. AF duration was related to mean<jats:italic>I<\/jats:italic><jats:sub>Na<\/jats:sub>in each dog (<jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup>=.573,<jats:italic>P<\/jats:italic>&lt;.001). We conclude that rapid atrial activation significantly reduces both conduction velocity and<jats:italic>I<\/jats:italic><jats:sub>Na<\/jats:sub>density. Since<jats:italic>I<\/jats:italic><jats:sub>Na<\/jats:sub>is a major determinant of conduction velocity, our data point to<jats:italic>I<\/jats:italic><jats:sub>Na<\/jats:sub>reduction as a potentially important mechanism contributing to the substrate for AF in this model.<\/jats:p>","DOI":"10.1161\/01.res.81.6.1045","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:47:05Z","timestamp":1339462025000},"page":"1045-1052","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":170,"title":["Tachycardia-Induced Changes in Na<sup>+<\/sup>Current in a Chronic Dog Model of Atrial Fibrillation"],"prefix":"10.1161","volume":"81","author":[{"given":"Rania","family":"Gaspo","sequence":"first","affiliation":[{"name":"From the Department of Medicine and Research Center, Montreal Heart Institute (R.G., R.F.B., E.B.-A., S.N.); the University of Montreal (S.N.); and the Department of Pharmacology and Therapeutics, McGill University (S.N.), Montreal, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph F.","family":"Bosch","sequence":"additional","affiliation":[{"name":"From the Department of Medicine and Research Center, Montreal Heart Institute (R.G., R.F.B., E.B.-A., S.N.); the University of Montreal (S.N.); and the Department of Pharmacology and Therapeutics, McGill University (S.N.), Montreal, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Bou-Abboud","sequence":"additional","affiliation":[{"name":"From the Department of Medicine and Research Center, Montreal Heart Institute (R.G., R.F.B., E.B.-A., S.N.); the University of Montreal (S.N.); and the Department of Pharmacology and Therapeutics, McGill University (S.N.), Montreal, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley","family":"Nattel","sequence":"additional","affiliation":[{"name":"From the Department of Medicine and Research Center, Montreal Heart Institute (R.G., R.F.B., E.B.-A., S.N.); the University of Montreal (S.N.); and the Department of Pharmacology and Therapeutics, McGill University (S.N.), Montreal, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","unstructured":"Kannel WB Wolf PA. 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