{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T14:28:46Z","timestamp":1777386526127,"version":"3.51.4"},"reference-count":43,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2014,7,15]]},"abstract":"<jats:p> Action potential duration alternans (APD-ALT), defined as long-short-long repetitive pattern of APD, potentially leads to lethal ventricular arrhythmia. However, the mechanisms of APD-ALT in the arrhythmogenesis of cardiac hypertrophy remain undetermined. Ca<jats:sup>2+<\/jats:sup>\/calmodulin-dependent protein kinase II (CaMKII) is known to modulate the function of cardiac sarcoplasmic reticulum and play an important role in Ca<jats:sup>2+<\/jats:sup> cycling. We thus aimed to determine the role of CaMKII in the increased susceptibility to APD-ALT and arrhythmogenesis in the hypertrophied heart. APD was measured by high-resolution optical mapping in left ventricular (LV) anterior wall from normotensive Wistar-Kyoto (WKY; n = 10) and spontaneously hypertensive rats (SHR; n = 10) during rapid ventricular pacing. APD-ALT was evoked at significantly lower pacing rate in SHR compared with WKY (382 \u00b1 43 vs. 465 \u00b1 45 beats\/min, P &lt; 0.01). These changes in APD-ALT in SHR were completely reversed by KN-93 (1 \u03bcmol\/l; n = 5), an inhibitor of CaMKII, but not its inactive analog, KN-92 (1 \u03bcmol\/l; n = 5). The magnitude of APD-ALT was also significantly greater in SHR than WKY and was completely normalized by KN-93. Ventricular fibrillation (VF) was induced by rapid pacing more frequently in SHR than in WKY (60 vs. 10%; P &lt; 0.05), which was also abolished by KN-93 (0%, P &lt; 0.05). Western blot analyses indicated that the CaMKII autophosphorylation at Thr287 was significantly increased in SHR compared with WKY. The increased susceptibility to APD-ALT and VF during rapid pacing in hypertrophied heart was prevented by KN-93. CaMKII could be an important mechanism of arrhythmogenesis in cardiac hypertrophy. <\/jats:p>","DOI":"10.1152\/ajpheart.00387.2012","type":"journal-article","created":{"date-parts":[[2014,5,24]],"date-time":"2014-05-24T05:51:38Z","timestamp":1400910698000},"page":"H199-H206","source":"Crossref","is-referenced-by-count":17,"title":["Ca<sup>2+<\/sup>\/calmodulin-dependent protein kinase II increases the susceptibility to the arrhythmogenic action potential alternans in spontaneously hypertensive rats"],"prefix":"10.1152","volume":"307","author":[{"given":"Hirofumi","family":"Mitsuyama","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisashi","family":"Yokoshiki","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, 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