期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 53, 期 6, 页码 880-890出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2012.10.003
关键词
Rgs5; Arrhythmia; Repolarization; K+ currents
资金
- National Key Basic Research Development Program (The 973 Program) [2012CB518604]
- National Natural Science Foundation of China [81070142, 81100129]
- Fundamental Research Funds for the Central Universities [201130202020003]
The aim of this study was to elucidate the effects of regulator of G-protein signaling 5 (Rgs5), a negative regulator of G-protein-mediated signaling, on cardiac repolarization and arrhythmia in mice. Wild-type and Rgs5(-/-) mice were subjected to in vivo, in vitro, and cellular electrophysiological experiments. Rgs5(-/-) mouse hearts showed significantly prolonged cardiac repolarization, including prolonged QT interval and action potential duration (APD). Consistent with these findings, measurement of K+ currents in ventricular myocytes of Rgs5(-/-) mice revealed significant reduction of the outward voltage-dependent K+ currents, including I-peak, I-to, I-Kur, and I-ss, compared to that in wild-type mice. Transcript and protein expression levels of Kv4.2, Kv4.3, Kv1.5, and Kv2.1 were downregulated in Rgs5(-/-) mouse ventricles compared with those in wild-type mice (P<0.05). In addition, electrically induced ventricular tachyarrhythmias were facilitated by Rgs5(-/-) in isolated hearts. Importantly, the increased incidence and duration of electrically induced ventricular tachyarrhythmias were associated with enhanced dispersion of APD and spatial heterogeneity of I-peak. I-to and I-Kur between the epicardium and endocardium in the Rgs5(-/-) heart. This study showed the relationship between the absence of Rgs5 and cardiac electrophysiological abnormality. The results strongly indicate that Rgs5(-/-) induced prolonged repolarization and ventricular tachyarrhythmia, which were closely related to the remodeling of voltage-dependent K+ currents. (C) 2012 Elsevier Ltd. All rights reserved.
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