{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T15:26:49Z","timestamp":1791127609647,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2007,9,11]],"date-time":"2007-09-11T00:00:00Z","timestamp":1189468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cardiovasc electrophysiol"],"published-print":{"date-parts":[[2007,11]]},"abstract":"<jats:p><jats:italic>Introduction:<\/jats:italic>It has been speculated that pacemaker current (I<jats:italic><jats:sub>f<\/jats:sub><\/jats:italic>) in human atria could play a role in causing ectopic atrial automaticity. Ivabradine is a novel selective and specific I<jats:italic><jats:sub>f<\/jats:sub><\/jats:italic>inhibitor in the sinus node that reduces heart rate without any negative inotropic effect. The aim of the study was to explore possible effects of ivabradine on I<jats:italic><jats:sub>f<\/jats:sub><\/jats:italic>in atrial myocytes.<\/jats:p><jats:p><jats:italic>Methods and Results:\u2002<\/jats:italic>Using patch\u2010clamp technique, we studied effects of ivabradine on I<jats:italic><jats:sub>f<\/jats:sub><\/jats:italic>present in atrial myocytes isolated from human right appendages of patients undergoing cardiac surgery. The identification of HCN isoforms was obtained by means of multiplex single\u2010cell RT\u2010PCR. Ivabradine induced a marked concentration and use\u2010dependent I<jats:italic><jats:sub>f<\/jats:sub><\/jats:italic>inhibition with an IC<jats:sub>50<\/jats:sub>at steady state of 2.9 \u03bcM. Time constant of block development (Tau<jats:sub>on<\/jats:sub>) decreases with the increase in the ivabradine concentration. Use\u2010dependent inhibition induced by ivabradine (3 \u03bcM) was not modified in the presence of cAMP (10 \u03bcM) in the pipette solution. Multiplex single\u2010cell RT\u2010PCR indicates that the major HCN gene subtype detected in atria was HCN2. HCN4 is detected weakly and HCN1 is not significantly detected.<\/jats:p><jats:p><jats:italic>Conclusions:\u2002<\/jats:italic>Ivabradine inhibits I<jats:italic><jats:sub>f<\/jats:sub><\/jats:italic>current in the nonpacemaker cell with characteristics similar to those described previously in rabbit sinus node cells, but revealed a lesser sensitivity for I<jats:italic><jats:sub>f<\/jats:sub><\/jats:italic>recorded in human atrial cell than hHCN4 subunits considered as the major contributors to native<jats:italic>f<\/jats:italic>\u2010channels in human sinoatrial node. A potential protection of atrial arrhythmias by ivabradine is discussed.<\/jats:p>","DOI":"10.1111\/j.1540-8167.2007.00955.x","type":"journal-article","created":{"date-parts":[[2007,9,16]],"date-time":"2007-09-16T04:49:50Z","timestamp":1189918190000},"page":"1190-1196","source":"Crossref","is-referenced-by-count":32,"title":["The Heart Rate\u2010Lowering Agent Ivabradine Inhibits the Pacemaker Current I<i><sub>f<\/sub><\/i>in Human Atrial Myocytes"],"prefix":"10.1111","volume":"18","author":[{"given":"ANTOUN","family":"EL 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