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

Song, Kai; Zhong, Xing-Guo; Xia, Xianming; Huang, Junhao; Fan, Yunlong; Yuan, Ren-Xiang; Xue, Nairui; Du, Juan; Han, Wenxiu; Xu, Aman; Shen, Bing

doi:10.1016/j.bbrc.2015.09.049

Cited by 22 publications

(25 citation statements)

References 26 publications

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“…Furthermore, our study also demonstrated that Orai1 could form a signaling complex with SK3, modulating SOCE and its associated membrane hyperpolarization in gallbladder smooth muscle (Song et al. ). However, whether Orai1 interacts with BK Ca in VSMCs is still unknown.…”

Section: Introductionsupporting

confidence: 60%

“…Recently, one study showed that Orai1 forms complex with SK3 in lipid rafts to control constitutive Ca 2+ entry and cancer cell migration, as well as bone metastasis (Chantome et al 2013). Furthermore, our study also demonstrated that Orai1 could form a signaling complex with SK3, modulating SOCE and its associated membrane hyperpolarization in gallbladder smooth muscle (Song et al 2015). However, whether Orai1 interacts with BK Ca in VSMCs is still unknown.…”

Section: Introductionmentioning

confidence: 59%

“…Our recent study also demonstrated that Orai1 could form a signaling complex with SK3 to control SOCE and its associated membrane hyperpolarization in gallbladder smooth muscle (Song et al. ). In this study, we for the first time demonstrated that Orai1 physically interacts with BK Ca in VSMCs of rat mesenteric arteries to regulate muscle contraction.…”

Section: Discussionmentioning

confidence: 84%

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Orai1 forms a signal complex with BK_C _a channel in mesenteric artery smooth muscle cells

Chen

Jiang³

et al. 2016

Physiol Rep

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Orai1, a specific nonvoltage‐gated Ca2+ channel, has been found to be one of key molecules involved in store‐operated Ca2+ 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 Ca2+‐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. Ca2+ 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.

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Section: Introductionsupporting

confidence: 60%

Section: Introductionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 84%

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Orai1 forms a signal complex with BK_C _a channel in mesenteric artery smooth muscle cells

Chen

Jiang³

et al. 2016

Physiol Rep

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“…These data suggest that agonistinduced Ca 2ϩ influx is likely due to a functional interaction/ communication between TRPC1-and Orai1-dependent SOCC and Ca V 1.2 channels in VSMC. Recently, independent studies showed that Orai1 associates with other channels to form the arachidonate-regulated Ca 2ϩ (ARC) channels (36), associates with TRPC1 to form non-selective SOCC (8,37), or even associates with small conductance Ca 2ϩ -activated potassium channel 3 (SK3) (11). Therefore, we provided several lines of evidence demonstrating that the SOCC components, Orai1 and TRPC1, form a macromolecular complex with Ca V 1.2 LTCC to regulate [Ca 2ϩ ] i signaling and vascular tone.…”

Section: Discussionmentioning

confidence: 99%

Orai1 and TRPC1 Proteins Co-localize with CaV1.2 Channels to Form a Signal Complex in Vascular Smooth Muscle Cells

Ávila-Médina

Calderón-Sánchez

González‐Rodríguez³

et al. 2016

Journal of Biological Chemistry

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Voltage-dependent Ca1.2 L-type Ca channels (LTCC) are the main route for calcium entry in vascular smooth muscle cells (VSMC). Several studies have also determined the relevant role of store-operated Ca channels (SOCC) in vascular tone regulation. Nevertheless, the role of Orai1- and TRPC1-dependent SOCC in vascular tone regulation and their possible interaction with Ca1.2 are still unknown. The current study sought to characterize the co-activation of SOCC and LTCC upon stimulation by agonists, and to determine the possible crosstalk between Orai1, TRPC1, and Ca1.2. Aorta rings and isolated VSMC obtained from wild type or smooth muscle-selective conditional Ca1.2 knock-out (Ca1.2) mice were used to study vascular contractility, intracellular Ca mobilization, and distribution of ion channels. We found that serotonin (5-HT) or store depletion with thapsigargin (TG) enhanced intracellular free Ca concentration ([Ca]) and stimulated aorta contraction. These responses were sensitive to LTCC and SOCC inhibitors. Also, 5-HT- and TG-induced responses were significantly attenuated in Ca1.2 mice. Furthermore, hyperpolarization induced with cromakalim or valinomycin significantly reduced both 5-HT and TG responses, whereas these responses were enhanced with LTCC agonist Bay-K-8644. Interestingly, in situ proximity ligation assay revealed that Ca1.2 interacts with Orai1 and TRPC1 in untreated VSMC. These interactions enhanced significantly after stimulation of cells with 5-HT and TG. Therefore, these data indicate for the first time a functional interaction between Orai1, TRPC1, and Ca1.2 channels in VSMC, confirming that upon agonist stimulation, vessel contraction involves Ca entry due to co-activation of Orai1- and TRPC1-dependent SOCC and LTCC.

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“…The contractile tension was measured as described previously . Briefly, tracheal rings were transferred to an organ bath containing Krebs‐Henseleit solution (pH 7.4) saturated with 95% O 2 plus 5% CO 2 at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Inflammatory cytokines tumour necrosis factor‐α and interleukin‐8 enhance airway smooth muscle contraction by increasing L‐type Ca²⁺ channel expression

Ding

Zhang

et al. 2018

Clin Exp Pharma Physio

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Inflammation elevates intracellular calcium concentrations ([Ca ] ) in airway smooth muscle (ASM). The L-type Ca channel (L-VDCC) plays an important role in regulating Ca influx in ASM. However, the role of L-VDCC in the inflammatory cytokine-induced pathology of ASM remains unclear. In the present study, we used calcium imaging and isometric tension measurements to assess the role of L-VDCC in agonist-induced [Ca ] rise and the associated contractions in mouse ASM, and we used immunoblotting to identify L-VDCC protein expression levels in mouse ASM after exposure to tumour necrosis factor alpha (TNF-α) or interleukin-8 (IL-8). Our results showed that high-K - or carbachol-induced contractions of mouse ASM were significantly greater after pretreatment with TNF-α or IL-8 for 24 hours. Both verapamil and nifedipine, L-VDCC inhibitors, abolished this increased contraction induced by TNF-α or IL-8 pretreatment. Moreover, TNF-α treatment enhanced carbachol-induced Ca influx in ASM cells, and this effect was abrogated by verapamil. Additionally, immunoblotting results showed that preincubation of mouse ASM with TNF-α or IL-8 also enhanced L-VDCC protein expression. On the basis of these findings, we concluded that proinflammatory cytokines, such as TNF-α and IL-8, increase the expression level of L-VDCC, which in turn contributes to augmented agonist-induced ASM contractions. This effect of inflammation on L-VDCC expression in ASM may be associated with airway hyper-responsiveness and involved in the development of asthma.

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

Cited by 22 publications

References 26 publications

Orai1 forms a signal complex with BK_C _a channel in mesenteric artery smooth muscle cells

Orai1 forms a signal complex with BK_C _a channel in mesenteric artery smooth muscle cells

Orai1 and TRPC1 Proteins Co-localize with CaV1.2 Channels to Form a Signal Complex in Vascular Smooth Muscle Cells

Inflammatory cytokines tumour necrosis factor‐α and interleukin‐8 enhance airway smooth muscle contraction by increasing L‐type Ca²⁺ channel expression

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

Cited by 22 publications

References 26 publications

Orai1 forms a signal complex with BKC a channel in mesenteric artery smooth muscle cells

Orai1 forms a signal complex with BKC a channel in mesenteric artery smooth muscle cells

Orai1 and TRPC1 Proteins Co-localize with CaV1.2 Channels to Form a Signal Complex in Vascular Smooth Muscle Cells

Inflammatory cytokines tumour necrosis factor‐α and interleukin‐8 enhance airway smooth muscle contraction by increasing L‐type Ca2+ channel expression

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Orai1 forms a signal complex with BK_C _a channel in mesenteric artery smooth muscle cells

Orai1 forms a signal complex with BK_C _a channel in mesenteric artery smooth muscle cells

Inflammatory cytokines tumour necrosis factor‐α and interleukin‐8 enhance airway smooth muscle contraction by increasing L‐type Ca²⁺ channel expression