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Orai1 forms a signal complex with SK3 channel in gallbladder smooth muscle

Song, Kai, Zhong, Xing-Guo, Xia, Xian-Ming, Huang, Jun-Hao, Fan, Yi-Fei, Yuan, Ren-Xiang, Xue, Nai-Rui, Du, Juan, Han, Wen-Xiu, Xu, A-Man, Shen, Bing
Biochemical and biophysical research communications 2015 v.466 pp. 456-462
RNA interference, agonists, calcium, gall bladder, guinea pigs, muscle strength, potassium channels, precipitin tests, small interfering RNA, smooth muscle
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.