title: Overexpression of microRNA-1 causes atrioventricular block in rodents.
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 (I Ca,L) and inward rectifier K(+) current (I K1). Expression of connexin 43 (Cx43) protein was determined by western blot analysis. Alternations of [Ca(2+)]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 I Ca,L was lower in ventricular myocytes from miR-1 Tg mice as compared with WT mice. Similarly, the current density of I K1 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 [Ca(2+)]i in ventricular myocytes but a prominent increase of the resting [Ca(2+)]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.
authors.affiliation: 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.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lihua
authors.initials: L
authors.lastname: Sun
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Haihai
authors.initials: H
authors.lastname: Liang
authors.forename: Xuelian
authors.initials: X
authors.lastname: Li
authors.forename: Ruijun
authors.initials: R
authors.lastname: Cai
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Weijie
authors.initials: W
authors.lastname: Du
authors.forename: Ruixue
authors.initials: R
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Wang
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.forename: Xidi
authors.initials: X
authors.lastname: Wang
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Du
authors.forename: Baofeng
authors.initials: B
authors.lastname: Yang
authors.forename: Xu
authors.initials: X
authors.lastname: Gao
authors.forename: Hongli
authors.initials: H
authors.lastname: Shan
mesh_terms: D000818:Animals; D054537:Atrioventricular Block / Q000209:etiology* / Q000235:genetics; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D018031:Connexin 43 / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D004562:Electrocardiography; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000378:metabolism*; D018613:Microscopy, Confocal; D017202:Myocardial Ischemia / Q000503:physiopathology*; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018031:Connexin 43; D017931:DNA Primers; D035683:MicroRNAs; C517731:Mirn1 microRNA, mouse; D024661:Potassium Channels, Inwardly Rectifying; D002118:Calcium
keywords: L-type calcium current ICa,L; atrioventricular block (AVB); connexin 43.; inward rectifier K+ current IK1; miR-1