Downregulation of Kv4.2 and Kv4.3 channel gene expression in right ventricular hypertrophy induced by monocrotaline in rat

Tian-tai Zhang, Bing Cui, De-zai Dai
Acta Pharmacologica Sinica 2004, 25 (2): 226-30

AIM: To investigate the differences in gene expression of transient outward potassium ion channel between the free wall of right ventricle, free wall of left ventricle, and the septum in monocrotaline (MCT)-induced right ventricular hypertrophy of rat.

METHODS: Twenty rats were randomly divided into two groups: a single injection of monocrotaline (MCT) 60 mg/kg (model) or saline (control). Four weeks later, hemodynamic parameters were measured and the gene expression of Ito channels were detected by semi-quantitative RT-PCR.

RESULTS: After 28 d, the right ventricular systolic pressure and central venous pressure were remarkably elevated by 128% and 533% in the MCT-treated group, accompanied by an overt right ventricle (RV) remodeling. The difference of mRNA expression of Kv1.4 was not significant in free wall of RV, left ventricle (LV), and septum in MCT group compared with control group. In contrast, mRNA of Kv4.2 and Kv4.3 in the free wall of RV in MCT-induced rat was dramatically decreased by 45.2% and 51.1% vs control, however, in free wall of LV and septum, no difference was found. In addition, mRNA expression level of Kv4.2 in control rat was significantly lower in septum than that in free wall of RV and LV.

CONCLUSION: Expression of Kv1.4, Kv4.2, and Kv4.3 differs between regions in normal rat hearts. The down-regulation of Kv4 family gene expression of Ito contributed to the pathophysiological changes in ventricular hypertrophy and pulmonary hypertension induced by MCT.

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