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Int J Biol Sci 2012; 8(2):236-248. doi:10.7150/ijbs.8.236 This issue Cite

Research Paper

Simvastatin Modulates Remodeling of Kv4.3 Expression in Rat Hypertrophied Cardiomyocytes

Feifei Su^1*, Miaoqian Shi^1*, Zhiqiang Yan², Dongbo Ou ¹, Juntang Li ³, Zifan Lu⁴, Qiangsun Zheng^{1 ✉}

1. Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
2. Department of Neurosurgery, Urumqi General Hospital of Lanzhou Military Command, Urumqi 830000, China
3. Department of Immunology, Fourth Military Medical University, Xi'an 710033, China
4. Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an 710032, China
^* These authors contributed equally to this work.

✉ Corresponding author: Qiangsun Zheng, M.D., Ph.D., Department of Cardiology and Arrhythmologic Center, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China. Telephone: +86 29 84777422; Fax: +86 29 84777422; Email: sufeifeiedu.cn More

Abstract

Objectives: Hypertrophy has been shown to be associated with arrhythmias which can be caused by abnormal remodeling of the Kv4-family of transient potassium channels. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) have recently been shown to exert pleiotropic protective effects in cardiovascular diseases, including anti-arrhythmias. It is hypothesized that remodeling of Kv4.3 occurs in rat hypertrophied cardiomyocytes and is regulated by simvastatin.

Methods: Male Sprague-Dawley rats and neonatal rat ventricular myocytes (NRVMs) underwent abdominal aortic banding (AAB) for 7 weeks and angiotensin II (AngII) treatment, respectively, to induce cardiac hypertrophy. Kv4.3 expression by NRVMs and myocardium (subepicardial and subendocardial) in the left ventricle was measured. The transient outward potassium current (I_to) of NRVMs was recorded using a whole-cell patch-clamp method.

Results: Expression of the Kv4.3 transcript and protein was significantly reduced in myocardium (subepicardial and subendocardial) in the left ventricle and in NRVMs. Simvastatin partially prevented the reduction of Kv4.3 expression in NRVMs and subepicardial myocardium but not in the subendocardial myocardium. Hypertrophied NRVMs exhibited a significant reduction in the I_to current and this effect was partially reversed by simvastatin.

Conclusions: Simvastatin alleviated the reduction of Kv4.3 expression, I_to currents in hypertrophied NRVMs and alleviated the reduced Kv4.3 expression in subepicardial myocardium from the hypertrophied left ventricle. It can be speculated that among the pleiotropic effects of simvastatin, the anti-arrhythmia effect is partly mediated by its effect on Kv4.3.

Keywords: Potassium channels, Kv4.3, arrhythmias, hydroxymethylglutaryl-CoA reductase inhibitors, hypertrophy.

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