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

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YE Hong(Department of Pathophysiology Key Laboratory of Pulmonary Diseases, Ministry of Health of China)
MA Wan-Li(Department of Pathophysiology Department of Respiratory Medicine in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China)
JIN Si(Department of Pathophysiology Key Laboratory of Pulmonary Diseases, Ministry of Health of China)
LIU Sheng-Yuan(Department of Pathophysiology Key Laboratory of Pulmonary Diseases, Ministry of Health of China)
WANG Di-Xun(Department of Pathophysiology Key Laboratory of Pulmonary Diseases, Ministry of Health of China)
HU Qing-Hua(Department of Pathophysiology Key Laboratory of Pulmonary Diseases, Ministry of Health of China)
Journal Title:
Volume 60, Issue 06, 2008
Key Word:
bronchus;myocyte;cigarette smoke extract;potassium channel;protein kinase C

Abstract: Large-conductance calcium-activated potassium channel (BKCa) and voltage-gated potassium channel Kv 1.5 play an important role in the pathogenesis of bronchial hyperresponsiveness (BHR). It is known that cigarette smoke can induce BHR, however, the role of BKCa 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 BKCa 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 BKCa and Kv1.5 a-subunits were determined by semi-quantitative RT-PCR and Western blot, respectively. The results showed that 5% CSE induced the translocation of PKCε, PKη, PKCθ from soluble fraction to particulate fraction, and reduced mRNA and protein expressions of BKCa and Kv1.5 a-subunits. The decreased expression of potassium channels was partly restored by PKC inhibitor, BIM or Goe6983. In summary, CSE may activate PKC isoforms ε,η,θ, thereby down-regulate the expressions of BKCa and Kv1.5 in BSMCs.

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