PMID- 27535226
OWN - NLM
STAT- MEDLINE
DCOM- 20170519
LR  - 20210209
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 291
IP  - 40
DP  - 2016 Sep 30
TI  - Orai1 and TRPC1 Proteins Co-localize with CaV1.2 Channels to Form a Signal 
      Complex in Vascular Smooth Muscle Cells.
PG  - 21148-21159
AB  - Voltage-dependent Ca(V)1.2 L-type Ca(2+) 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(2+) channels (SOCC) in vascular 
      tone regulation. Nevertheless, the role of Orai1- and TRPC1-dependent SOCC in 
      vascular tone regulation and their possible interaction with Ca(V)1.2 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 Ca(V)1.2. Aorta rings and isolated VSMC obtained from 
      wild type or smooth muscle-selective conditional Ca(V)1.2 knock-out 
      (Ca(V)1.2(KO)) mice were used to study vascular contractility, intracellular 
      Ca(2+) mobilization, and distribution of ion channels. We found that serotonin 
      (5-HT) or store depletion with thapsigargin (TG) enhanced intracellular free 
      Ca(2+) concentration ([Ca(2+)](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 Ca(V)1.2(KO) 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 
      Ca(V)1.2 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 Ca(V)1.2 channels in VSMC, confirming that upon agonist stimulation, 
      vessel contraction involves Ca(2+) entry due to co-activation of Orai1- and 
      TRPC1-dependent SOCC and LTCC.
CI  - (c) 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
FAU - Avila-Medina, Javier
AU  - Avila-Medina J
AD  - From the Departamento de Fisiologia Medica y Biofisica and Groupo de 
      Fisiopatologia Cardiovascular, Instituto de Biomedicina de Sevilla (IBiS), 
      Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, 41013 
      Sevilla, Spain.
FAU - Calderon-Sanchez, Eva
AU  - Calderon-Sanchez E
AD  - Groupo de Fisiopatologia Cardiovascular, Instituto de Biomedicina de Sevilla 
      (IBiS), Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, 
      41013 Sevilla, Spain.
FAU - Gonzalez-Rodriguez, Patricia
AU  - Gonzalez-Rodriguez P
AD  - From the Departamento de Fisiologia Medica y Biofisica and.
FAU - Monje-Quiroga, Francisco
AU  - Monje-Quiroga F
AD  - the Department of Neurophysiology and Neuropharmacology, Center for Physiology 
      and Pharmacology, Medical University of Vienna, 1090 Wien, Austria, and.
FAU - Rosado, Juan Antonio
AU  - Rosado JA
AD  - the Departamento de Fisiologia, Universidad de Extremadura, 10071 Caceres, Spain.
FAU - Castellano, Antonio
AU  - Castellano A
AD  - From the Departamento de Fisiologia Medica y Biofisica and.
FAU - Ordonez, Antonio
AU  - Ordonez A
AD  - Groupo de Fisiopatologia Cardiovascular, Instituto de Biomedicina de Sevilla 
      (IBiS), Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, 
      41013 Sevilla, Spain.
FAU - Smani, Tarik
AU  - Smani T
AD  - From the Departamento de Fisiologia Medica y Biofisica and Groupo de 
      Fisiopatologia Cardiovascular, Instituto de Biomedicina de Sevilla (IBiS), 
      Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, 41013 
      Sevilla, Spain, tasmani@us.es.
LA  - eng
PT  - Journal Article
DEP - 20160817
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (CACNA1C protein, mouse)
RN  - 0 (Calcium Channels, L-Type)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (ORAI1 Protein)
RN  - 0 (Orai1 protein, mouse)
RN  - 0 (TRPC Cation Channels)
RN  - 0 (transient receptor potential cation channel, subfamily C, member 1)
RN  - 333DO1RDJY (Serotonin)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Aorta/cytology/*metabolism
MH  - Calcium/metabolism
MH  - Calcium Channels, L-Type/genetics/*metabolism
MH  - Calcium Signaling/*physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Multiprotein Complexes/genetics/metabolism
MH  - Muscle, Smooth, Vascular/cytology/*metabolism
MH  - Myocytes, Smooth Muscle/cytology/*metabolism
MH  - ORAI1 Protein/genetics/*metabolism
MH  - Serotonin/metabolism
MH  - TRPC Cation Channels/genetics/*metabolism
MH  - Vasoconstriction/physiology
PMC - PMC5076523
OTO - NOTNLM
OT  - CaV1.2
OT  - CaV1.2 channel
OT  - Orai1
OT  - TRPC1
OT  - Vascular tone regulation
OT  - calcium
OT  - calcium release-activated calcium channel protein 1 (ORAI1)
OT  - excitation-contraction coupling (E-C coupling)
OT  - ion channel
OT  - vascular smooth muscle cells
EDAT- 2016/08/19 06:00
MHDA- 2017/05/20 06:00
PMCR- 2017/09/30
CRDT- 2016/08/19 06:00
PHST- 2016/06/10 00:00 [received]
PHST- 2016/08/19 06:00 [pubmed]
PHST- 2017/05/20 06:00 [medline]
PHST- 2016/08/19 06:00 [entrez]
PHST- 2017/09/30 00:00 [pmc-release]
AID - S0021-9258(20)35891-9 [pii]
AID - M116.742171 [pii]
AID - 10.1074/jbc.M116.742171 [doi]
PST - ppublish
SO  - J Biol Chem. 2016 Sep 30;291(40):21148-21159. doi: 10.1074/jbc.M116.742171. Epub 
      2016 Aug 17.