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Cigarette smoke extract activates PKC isoforms and down--regulates the expressions of potassium channels BK_(Ca) and Kv1.5 in rat bronchial smooth muscle cells

Ye Hong, Ma Wanli, Jin Si, Liu Shengyuan, Wang Dixun, Hu Qinghua

Department of Pathophysiology,Key Laboratory of Pulmonary Diseases,Ministry of Health of China,Tongji Medical College,Huazhong University of Science and Technology.Wuhan 430030,Hubei；China

Abstract

Large-conductance calcium-activated potassium channel(BK_(Ca)) and voltage-gated potassium channel Kv1.5 play an impor-tant role in the pathogenesis of bronchial hyperresponsiveness(BHR).It is known that cigarette smoke can induce BHR,however,the role of BK_(Ca) and Kv1.5 expression in it remains to be further elucidated.The purpose of the present study was to investigate the direct effects of cigarette smoke extract(CSE) on BK_(Ca) and Kv1.5 expression,and the role of protein kinase C(PKC) isoforms activation in primary cultured rat bronchial smooth muscle cells(BSMCs).Primarily cultured rat BSMCs were treated with 5% CSE,the expression and translocation of PKC isoforms were measured by Western blot,and the mRNA and protein levels of BK_(Ca) and Kv1.5 #alpha#-subunits were determined by semi-quantitative RT-PCR and Western blot,respectively.The results showed that 5% CSE induced the translo-cation of PKC#epsilon#,PKC#eta#,PKC#thet# from soluble fraction to particulate fraction,and reduced mRNA and protein expressions of BK_(Ca) and Kv1.5 #alpha#-subunits.The decreased expression of potassium channels was partly restored by PKC inhibitor,BIM or Göe6983.In summary,CSE may activate PKC isoforms #epsilon#,#eta#,#thet#,thereby down-regulate the expressions of BK_(Ca) and Kv1.5 in BSMCs.

Key words: bronchus;myocyte;cigarette smoke extract;Potassium channel;Protein kinase C

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Citing This Article：

Ye Hong, Ma Wanli, Jin Si, Liu Shengyuan, Wang Dixun, Hu Qinghua. Cigarette smoke extract activates PKC isoforms and down--regulates the expressions of potassium channels BK_(Ca) and Kv1.5 in rat bronchial smooth muscle cells. Acta Physiol Sin 2008; 60 (6): 709-714 (in Chinese with English abstract).