Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10750846 | Biochemical and Biophysical Research Communications | 2015 | 7 Pages |
Abstract
Orai1 is one of the key components of store-operated Ca2+ entry (SOCE) involved in diverse physiological functions. Orai1 may associate with other proteins to form a signaling complex. In the present study, we investigated the interaction between Orai1 and small conductance Ca2+-activated potassium channel 3 (SK3). With the use of RNA interference technique, we found that the SOCE and its associated membrane hyperpolarization were reduced while Orai1 was knocked down by a specific Orai1 siRNA in guinea pig gallbladder smooth muscle. However, with the use of isometric tension measurements, our results revealed that agonist-induced muscle contractility was significantly enhanced after Orai1 protein was knocked down or the tissue was treated by SK3 inhibitor apamin, but not affected by larger conductance Ca2+-activated potassium channel inhibitor iberiotoxin or intermediate conductance Ca2+-activated potassium channel inhibitor TRAM-34. In addition, in the presence of apamin, Orai1 siRNA had no additional effect on agonist-induced contraction. In coimmunoprecipitation experiment, SK3 and Orai1 pulled down each other. These data suggest that, Orai1 physically associated with SK3 to form a signaling complex in gallbladder smooth muscle. Ca2+ entry via Orai1 activates SK3, resulting in membrane hyperpolarization in gallbladder smooth muscle. This hyperpolarizing effect of Orai1-SK3 coupling could serve to prevent excessive contraction of gallbladder smooth muscle in response to contractile agonists.
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Authors
Kai Song, Xing-Guo Zhong, Xian-Ming Xia, Jun-Hao Huang, Yi-Fei Fan, Ren-Xiang Yuan, Nai-Rui Xue, Juan Du, Wen-Xiu Han, A-Man Xu, Bing Shen,