Referenced in: none

Automatically associated channels: SK3

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

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

Journal, date & volume: Biochem. Biophys. Res. Commun., 2015 Oct 23 , 466, 456-62

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/26367175

Abstract
Orai1 is one of the key components of store-operated Ca(2+) 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 Ca(2+)-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 Ca(2+)-activated potassium channel inhibitor iberiotoxin or intermediate conductance Ca(2+)-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. Ca(2+) 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.