Orai1 forms a signal complex with SK3 channel in gallbladder smooth muscle
| Autor: | Nairui Xue, Kai Song, Ren-Xiang Yuan, Yi-Fei Fan, Wen-Xiu Han, Xian-Ming Xia, Juan Du, Bing Shen, Xing-Guo Zhong, A-Man Xu, Junhao Huang |
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| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty Small-Conductance Calcium-Activated Potassium Channels Guinea Pigs Biophysics Biology In Vitro Techniques Apamin Biochemistry Membrane Potentials chemistry.chemical_compound SK3 Internal medicine medicine Animals Calcium Signaling Molecular Biology Voltage-dependent calcium channel Gallbladder Muscle Smooth Cell Biology Membrane hyperpolarization Hyperpolarization (biology) Iberiotoxin Calcium Channel Blockers Potassium channel Calcium Channel Agonists Endocrinology chemistry Gene Knockdown Techniques Multiprotein Complexes RNA Interference Calcium Channels medicine.symptom Muscle contraction Muscle Contraction |
| Zdroj: | Biochemical and biophysical research communications. 466(3) |
| ISSN: | 1090-2104 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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