{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T11:10:02Z","timestamp":1745233802159,"version":"3.40.4"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,12,21]],"date-time":"2012-12-21T00:00:00Z","timestamp":1356048000000},"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":[[2013,4]]},"abstract":"<jats:p><jats:bold>CaMKII and Arrhythmias.<\/jats:bold>\u2002<jats:italic>Background:<\/jats:italic>CaMKII activation is proarrhythmic in heart failure where myocardium is stretched. However, the arrhythmogenic role of CaMKII in stretched ventricle has not been well understood.<\/jats:p><jats:p><jats:bold><jats:italic>Objective:<\/jats:italic><\/jats:bold>We tested abnormal impulse inducibility by stretch current in myocytes isolated from CaMKII\u03b4 knockout (KO) mouse left ventricle (LV) where CaMKII activity is reduced by \u2248 62%.<\/jats:p><jats:p><jats:bold><jats:italic>Methods and Results:<\/jats:italic><\/jats:bold>Action potentials were recorded by whole\u2010cell patch clamp, and abnormal impulses were induced in LV myocytes by a simulation of stretch\u2010activated channel (SAC) current. SAC activation failed to induce abnormal impulses in wild type (WT) myocytes but steadily produced early after\u2010depolarizations and automaticity in KO myocytes in which an increase in L\u2010type calcium channel (LTCC) current (I<jats:sub>Ca<\/jats:sub>) and a reduction of sarcoplasmic reticulum Ca<jats:sup>2+<\/jats:sup>leak and action potential duration (APD) were observed. The abnormal impulses were not suppressed by CaMKII inhibitor AIP whereas a low concentration of nifedipine eliminated abnormal impulses without shortening APD, implicating I<jats:sub>Ca<\/jats:sub>in promoting stretch\u2010induced abnormal impulses. In addition, APD prolongation by LTCC opener S(\u2010)Bay K 8644 or isoproterenol facilitated abnormal impulse induction in WT ventricular myocytes even in the presence of CaMKII inhibitor AIP, whereas APD prolongation by K<jats:sup>+<\/jats:sup>channel blocker 4\u2010aminopyridine promoted abnormal impulses in KO myocytes but not in WT myocytes.<\/jats:p><jats:p><jats:bold><jats:italic>Conclusion:<\/jats:italic><\/jats:bold>I<jats:sub>Ca<\/jats:sub>activation plays a central role in stretch\u2010induced abnormal impulses and APD prolongation is arrhythmogenic only when I<jats:sub>Ca<\/jats:sub>is highly activated. At increased I<jats:sub>Ca<\/jats:sub>activation, CaMKII inhibition cannot suppress abnormal impulse induction.<jats:italic>(J Cardiovasc Electrophysiol, Vol. 24, pp. 457\u2010463, April 2013)<\/jats:italic><\/jats:p>","DOI":"10.1111\/jce.12060","type":"journal-article","created":{"date-parts":[[2012,11,22]],"date-time":"2012-11-22T13:37:11Z","timestamp":1353591431000},"page":"457-463","source":"Crossref","is-referenced-by-count":3,"title":["Stretch Current\u2010Induced Abnormal Impulses in CaMKII\u03b4 Knockout Mouse Ventricular Myocytes"],"prefix":"10.1111","volume":"24","author":[{"given":"DONGWU","family":"LAI","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"LIN","family":"XU","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JUN","family":"CHENG","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ARNAUD 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