UMM Logo

Universitas Muhammadiyah Malang


Free Download Journals Directory


International Journal Of Bilogical Sciences

.: Home > International Journal Of Bilogical Sciences > 2013 > Volume 9 Number 5 > Yong Zhang1,2*, Lihua Sun1*, Yan Zhang1, Haihai Liang1, Xuelian Li1, Ruijun Cai1, Lu Wang1, Weijie Du1, Ruixue Zhang1, Jing Li1, Zhiguo Wang2, Ning Ma3, Xidi Wang3, Zhimin Du2, Baofeng Yang1,2, Xu Gao3,✉, Hongli Shan1,2,✉

Overexpression of microRNA-1 Causes Atrioventricular Block in Rodents

Yong Zhang1,2*, Lihua Sun1*, Yan Zhang1, Haihai Liang1, Xuelian Li1, Ruijun Cai1, Lu Wang1, Weijie Du1, Ruixue Zhang1, Jing Li1, Zhiguo Wang2, Ning Ma3, Xidi Wang3, Zhimin Du2, Baofeng Yang1,2, Xu Gao3,✉, Hongli Shan1,2,✉
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.
Abstract :

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.

Date Deposited : 11 Apr 2015 09:43

Last Modified : 11 Apr 2015 09:43

Official URL: http://www.ijbs.com/ms/archive

Volume 9, Number 5, - 2013 , ISSN 1449-2288

Download:
Full Text Original
Abstract : pdf doc