{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:44:31Z","timestamp":1791121471106,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,12,21]],"date-time":"2006-12-21T00:00:00Z","timestamp":1166659200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2007,1]]},"abstract":"<jats:p>Previous studies have suggested an important role for the inward rectifier K<jats:sup>+<\/jats:sup> current (<jats:italic>I<\/jats:italic><jats:sub>K1<\/jats:sub>) in stabilizing rotors responsible for ventricular tachycardia (VT) and fibrillation (VF). To test this hypothesis, we used a line of transgenic mice (TG) overexpressing Kir 2.1\u2013green fluorescent protein (GFP) fusion protein in a cardiac\u2010specific manner. Optical mapping of the epicardial surface in ventricles showed that the Langendorff\u2010perfused TG hearts were able to sustain stable VT\/VF for 350 \u00b1 1181 s at a very high dominant frequency (DF) of 44.6 \u00b1 4.3 Hz. In contrast, tachyarrhythmias in wild\u2010type hearts (WT) were short\u2010lived (3 \u00b1 9 s), and the DF was 26.3 \u00b1 5.2 Hz. The stable, high frequency, reentrant activity in TG hearts slowed down, and eventually terminated in the presence of 10 \u03bc<jats:sc>m<\/jats:sc> Ba<jats:sup>2+<\/jats:sup>, suggesting an important role for <jats:italic>I<\/jats:italic><jats:sub>K1<\/jats:sub>. Moreover, by increasing <jats:italic>I<\/jats:italic><jats:sub>K1<\/jats:sub> density in a two\u2010dimensional computer model having realistic mouse ionic and action potential properties, a highly stable, fast rotor (\u224845 Hz) could be induced. Simulations suggested that the TG hearts allowed such a fast and stable rotor because of both greater outward conductance at the core and shortened action potential duration in the core vicinity, as well as increased excitability, in part due to faster recovery of Na<jats:sup>+<\/jats:sup> current. The latter resulted in a larger rate of increase in the local conduction velocity as a function of the distance from the core in TG compared to WT hearts, in both simulations and experiments. Finally, simulations showed that rotor frequencies were more sensitive to changes (doubling) in <jats:italic>I<\/jats:italic><jats:sub>K1<\/jats:sub>, compared to other K<jats:sup>+<\/jats:sup> currents. In combination, these results provide the first direct evidence that <jats:italic>I<\/jats:italic><jats:sub>K1<\/jats:sub> up\u2010regulation in the mouse heart is a substrate for stable and very fast rotors.<\/jats:p>","DOI":"10.1113\/jphysiol.2006.121475","type":"journal-article","created":{"date-parts":[[2006,11,10]],"date-time":"2006-11-10T01:34:13Z","timestamp":1163122453000},"page":"315-326","source":"Crossref","is-referenced-by-count":138,"title":["Up\u2010regulation of the inward rectifier K<sup>+<\/sup> current (<i>I<\/i><sub>K1<\/sub>) in the mouse heart accelerates and stabilizes rotors"],"prefix":"10.1113","volume":"578","author":[{"given":"Sami F.","family":"Noujaim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep 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