Proarrhythmia in a non-failing murine model of cardiac-specific Na+/Ca 2+ exchanger overexpression: whole heart and cellular mechanisms.

Basic Research in Cardiology
Christian PottFrank U Müller

Abstract

The cardiac Na(+)/Ca(2+) exchanger (NCX) generates an inward electrical current during SR-Ca(2+) release, thus possibly promoting afterdepolarizations of the action potential (AP). We used transgenic mice 12.5 weeks or younger with cardiomyocyte-directed overexpression of NCX (NCX-Tg) to study the proarrhythmic potential and mechanisms of enhanced NCX activity. NCX-Tg exhibited normal echocardiographic left ventricular function and heart/body weight ratio, while the QT interval was prolonged in surface ECG recordings. Langendorff-perfused NCX-Tg, but not wild-type (WT) hearts, developed ventricular tachycardia. APs and ionic currents were measured in isolated cardiomyocytes. Cell capacitance was unaltered between groups. APs were prolonged in NCX-Tg versus WT myocytes along with voltage-activated K(+) currents (K(v)) not being reduced but even increased in amplitude. During abrupt changes in pacing cycle length, early afterdepolarizations (EADs) were frequently recorded in NCX-Tg but not in WT myocytes. Next to EADs, delayed afterdepolarizations (DAD) triggering spontaneous APs (sAPs) occurred in NCX-Tg but not in WT myocytes. To test whether sAPs were associated with spontaneous Ca(2+) release (sCR), Ca(2+) transients were rec...Continue Reading

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Citations

Nov 30, 2010·Herzschrittmachertherapie & Elektrophysiologie·C PottL Eckardt
Apr 27, 2013·Cardiovascular Research·Zhilin QuJames N Weiss
Nov 14, 2016·Journal of Molecular and Cellular Cardiology·N BögeholzC Pott
Jun 1, 2016·The Journal of Physiological Sciences : JPS·Mariana ArgenzianoEduardo Garcia Gras
Sep 23, 2014·Circulation. Arrhythmia and Electrophysiology·Andrew G EdwardsAndrew D McCulloch
Sep 5, 2015·Circulation. Arrhythmia and Electrophysiology·Nils BögeholzChristian Pott
Nov 12, 2016·American Journal of Physiology. Heart and Circulatory Physiology·Yasutaka KurataToshishige Shibamoto
Nov 15, 2018·Frontiers in Physiology·Shanna Hamilton, Dmitry Terentyev
Oct 30, 2021·Frontiers in Physiology·Andrew G EdwardsWilliam E Louch

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