Int J Biol Sci 2013; 9(5):455-462. doi:10.7150/ijbs.4630
Overexpression of microRNA-1 Causes Atrioventricular Block in Rodents
1. Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China;
2. Institute of Cardiovascular Research, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China;
3. Department of Biochemistry, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
* The first two authors made equal contribution to this work.
The present study was designed to investigate whether microRNAs (miRNAs) are involved in atrioventricular block (AVB) in the setting of myocardial ischemia (MI). A cardiac-specific miR-1 transgenic (Tg) mouse model was successfully established for the first time in this study using microinjection. miR-1 level was measured by real-time qRT-PCR. Whole-cell patch clamp was employed to record L-type calcium current (ICa,L) and inward rectifier K+ current (IK1). Expression of connexin 43 (Cx43) protein was determined by western blot analysis. Alternations of [Ca2+]i was detected by laser scanning confocal microscopy in ventricular myocytes. The incidence of AVB was higher in miR-1 Tg mice than that in wild-type (WT) mice. The normalized peak current amplitude of ICa,L was lower in ventricular myocytes from miR-1 Tg mice as compared with WT mice. Similarly, the current density of IK1 was decreased in miR-1 Tg mice than that in WT mice. Compared with WT mice, miR-1 Tg mice exhibited a significant decrease of the systolic [Ca2+]i in ventricular myocytes but a prominent increase of the resting [Ca2+]i. Moreover, Cx43 protein was downregulated in miR-1 Tg mice compared to that in WT mice. Administration of LNA-modified antimiR-1 reversed all the above changes. miR-1 overexpression may contribute to the increased susceptibility of the heart to AVB, which provides us novel insights into the molecular mechanisms underlying ischemic cardiac arrhythmias.
Keywords: atrioventricular block (AVB), miR-1, L-type calcium current ICa,L, inward rectifier K+ current IK1, connexin 43.
Zhang Y, Sun L, Zhang Y, Liang H, Li X, Cai R, Wang L, Du W, Zhang R, Li J, Wang Z, Ma N, Wang X, Du Z, Yang B, Gao X, Shan H. Overexpression of microRNA-1 Causes Atrioventricular Block in Rodents. Int J Biol Sci 2013; 9(5):455-462. doi:10.7150/ijbs.4630. Available from http://www.ijbs.com/v09p0455.htm