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Title: Orai1 and TRPC1 Proteins Co-localize with CaV1.2 Channels to Form a Signal Complex in Vascular Smooth Muscle Cells.
Authors: Ávila-Medina, Javier
Calderón-Sánchez, Eva
González-Rodríguez, Patricia
Monje-Quiroga, Francisco
Rosado, Juan Antonio
Castellano, Antonio
Ordóñez, Antonio
Smani, Tarik
Keywords: CaV1.2;CaV1.2 channel;Orai1;TRPC1;Vascular tone regulation;calcium;calcium release-activated calcium channel protein 1 (ORAI1);excitation-contraction coupling (E-C coupling);ion channel;vascular smooth muscle cells
metadata.dc.subject.mesh: Animals
Calcium Channels, L-Type
Calcium Signaling
Mice, Knockout
Multiprotein Complexes
Muscle, Smooth, Vascular
Myocytes, Smooth Muscle
ORAI1 Protein
TRPC Cation Channels
Issue Date: 17-Aug-2016
Abstract: Voltage-dependent CaV1.2 L-type Ca2+ 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 Ca2+ channels (SOCC) in vascular tone regulation. Nevertheless, the role of Orai1- and TRPC1-dependent SOCC in vascular tone regulation and their possible interaction with CaV1.2 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 CaV1.2. Aorta rings and isolated VSMC obtained from wild type or smooth muscle-selective conditional CaV1.2 knock-out (CaV1.2KO) mice were used to study vascular contractility, intracellular Ca2+ mobilization, and distribution of ion channels. We found that serotonin (5-HT) or store depletion with thapsigargin (TG) enhanced intracellular free Ca2+ concentration ([Ca2+]i) and stimulated aorta contraction. These responses were sensitive to LTCC and SOCC inhibitors. Also, 5-HT- and TG-induced responses were significantly attenuated in CaV1.2KO 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 CaV1.2 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 CaV1.2 channels in VSMC, confirming that upon agonist stimulation, vessel contraction involves Ca2+ entry due to co-activation of Orai1- and TRPC1-dependent SOCC and LTCC.
metadata.dc.identifier.doi: 10.1074/jbc.M116.742171
Appears in Collections:Producción 2020

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