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[Combined transgenic inhibition of CaMKII and Ik1 on cardiac remodeling.] [Article in Chinese]

HUANG Yun, DAI Miao, DU Yi-Mei, YAO Yu-Feng, ZHANG Jia-Ming, SU Guan-Hua, SHU Yan-Wen, CUI Tian-Pen, DU Xin-Ling, LI Jing-Dong

Department of Gerontology； Department of Cardiology, Union Hospital； Life Science College； Laboratory Medicine Center, the First Hospital of Wuhan； Department of Cardiac Surgery of Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China

Abstract

This study was aimed to establish an experimental mouse model of combined transgenic inhibition of both multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) and inward rectifier potassium current (Ik1), and to observe whether the specific inhibition of both CaMKII and Ik1 can bring about any effects on cardiac remodeling. Mice were divided into 4 groups: wild type (WT), CaMKII inhibited (AC3-I), Ik1 inhibited (Kir2.1-AAA) and combined inhibition of both CaMKII and Ik1 (AC3-I+Kir2.1-AAA). Mice in each group received electrocardiogram (ECG) and echocardiography examination. ECG in the condition of isoproterenol (ISO) injection was also checked. The whole cell patch clamp technique was used to measure Ik1 and the transient outward potassium current (Ito) from enzymatically isolated myocytes of left ventricle. In the condition of basal status, no significant changes of heart rate, PR interval and QRS interval were observed. No mouse showed ventricular arrhythmias in all of the 4 groups. After ISO injection, each group presented no significant ventricular arrhythmias either. The indexes measured by M-mode (motion-mode) and two-dimensional echocardiography had no significant differences among the four groups. Ik1 in AC3-I group was significantly higher than those in other three groups (P < 0.01) because of the results brought about by CaMKII inhibition. Among the latter three groups, both Kir2.1-AAA group and AC3-I+Kir2.1-AAA group had a significant reduced Ik1 compared with that of WT group, which was due to the Ik1 inhibition (P < 0.01). Ito in AC3-I group was higher than that of the other three groups (P < 0.01), but there were no significant differences in Ito among WT, Kir2.1-AAA and AC3-I+Kir2.1-AAA groups. Thus, combined transgenic myocardial CaMKII and Ik1 inhibition eliminated the up-regulation of Ik1 in CaMKII inhibited mice, and had no effects on cardiac remodeling including heart structure and function as well as arrhythmias at the basic and ISO conditions. The results of this study may provide a basis for the further investigation of combined inhibition of CaMKII and Ik1 in pathogenic cardiac remodeling.

Key words: CaMKII; Ik1; arrhythmias; cardiac remodeling

Received: 2014-10-11　　Accepted: 2015-01-02

Corresponding author: 李景东　　E-mail: jingdong-li@mail.hust.edu.cn

Citing This Article：

HUANG Yun, DAI Miao, DU Yi-Mei, YAO Yu-Feng, ZHANG Jia-Ming, SU Guan-Hua, SHU Yan-Wen, CUI Tian-Pen, DU Xin-Ling, LI Jing-Dong. [Combined transgenic inhibition of CaMKII and Ik1 on cardiac remodeling.] [Article in Chinese]. Acta Physiol Sin 2015; 67 (2): 201-206 (in Chinese with English abstract).