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.
Large-conductance calcium-activated potassium channel (BK(Ca)) and voltage-gated potassium channel Kv1.5 play an important role in the pathogenesis of bronchial hyperresponsiveness (BHR). It is known that cigarette smoke can induce BHR, however, the role of 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 translocation of PKCepsilon, PKCeta, PKCtheta 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 Goe6983. In summary, CSE may activate PKC isoforms epsilon, eta, theta, thereby down-regulate the expressions of BK(Ca) and Kv1.5 in BSMCs.
Ye
Hong
H
Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. yehmwl@yahoo.com.cn
Ma
Wan-Li
WL
Jin
Si
S
Liu
Sheng-Yuan
SY
Wang
Di-Xun
DX
Hu
Qing-Hua
QH
D000818:Animals; D001980:Bronchi / Q000166:cytology; D002478:Cells, Cultured; D051666:Kv1.5 Potassium Channel / Q000378:metabolism*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology*; D020033:Protein Isoforms / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana
D051666:Kv1.5 Potassium Channel; D051036:Large-Conductance Calcium-Activated Potassium Channels; D020033:Protein Isoforms; D012906:Smoke; D011493:Protein Kinase C