Orai1 forms a signal complex with BKCa channel in mesenteric artery smooth muscle cells.
Orai1, a specific nonvoltage-gated Ca(2+) channel, has been found to be one of key molecules involved in store-operated Ca(2+) entry (SOCE). Orai1 may associate with other proteins to form a signaling complex, which is essential for regulating a variety of physiological functions. In this study, we studied the possible interaction between Orai1 and large conductance Ca(2+)-activated potassium channel (BKC a). Using RNA interference technique, we demonstrated that the SOCE and its associated membrane hyperpolarization were markedly suppressed after knockdown of Orai1 with a specific Orai1 siRNA in rat mesenteric artery smooth muscle. Moreover, isometric tension measurements showed that agonist-induced vasocontraction was increased after Orai1 was knocked down or the tissue was incubated with BKC a blocker iberiotoxin. Coimmunoprecipitation data revealed that BKC a and Orai1 could reciprocally pull down each other. In situ proximity ligation assay further demonstrated that Orai1 and BKC a are in close proximity. Taken together, these results indicate that Orai1 physically associates with BKC a to form a signaling complex in the rat mesenteric artery smooth muscle. Ca(2+) influx via Orai1 stimulates BKC a, leading to membrane hyperpolarization. This hyperpolarizing effect of Orai1-BKC a coupling could contribute to reduce agonist-induced membrane depolarization, therefore preventing excessive contraction of the rat mesenteric artery smooth muscle in response to contractile agonists.
['Chen|Meihua|M|', 'Li|Jie|J|', 'Jiang|Feifei|F|', 'Fu|Jie|J|', 'Xia|Xianming|X|', 'Du|Juan|J|', 'Hu|Min|M|', 'Huang|Junhao|J|', 'Shen|Bing|B|']
D000818:Animals D015220:Calcium Channels D002478:Cells, Cultured D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits D008564:Membrane Potentials D008638:Mesenteric Arteries D009131:Muscle, Smooth, Vascular D032389:Myocytes, Smooth Muscle D000071740:ORAI1 Protein D009924:Organ Culture Techniques D010656:Phenylephrine D051381:Rats D017207:Rats, Sprague-Dawley D014661:Vasoconstriction
Orai1 mesenteric artery BKC
a store‐operated Ca2+ entry vascular smooth muscle cells