Evidence that Orai1 does not contribute to store-operated TRPC1 channels in vascular smooth muscle cells

Abstract: Ca2+-permeable store-operated channels (SOCs) mediate Ca2+ entry pathways which are involved in many cellular functions such as contraction, growth, and proliferation. Prototypical SOCs are formed of Orai1 proteins and are activated by the endo/sarcoplasmic reticulum Ca2+ sensor stromal in...

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Autores principales: Shi, Jian, Miralles, Francesc, Kinet, Jean-Pierre, Birnbaumer, Lutz, Large, William A., Albert, Anthony P.
Formato: Artículo
Lenguaje:Inglés
Publicado: Taylor & Francis 2019
Materias:
CALCIO
MEMBRANA CELULAR
PROTEINAS
MUSCULOS
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/8727
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139123456789-8727
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic CALCIO
MEMBRANA CELULAR
PROTEINAS
MUSCULOS
spellingShingle CALCIO
MEMBRANA CELULAR
PROTEINAS
MUSCULOS
Shi, Jian
Miralles, Francesc
Kinet, Jean-Pierre
Birnbaumer, Lutz
Large, William A.
Albert, Anthony P.
Evidence that Orai1 does not contribute to store-operated TRPC1 channels in vascular smooth muscle cells
topic_facet CALCIO
MEMBRANA CELULAR
PROTEINAS
MUSCULOS
description Abstract: Ca2+-permeable store-operated channels (SOCs) mediate Ca2+ entry pathways which are involved in many cellular functions such as contraction, growth, and proliferation. Prototypical SOCs are formed of Orai1 proteins and are activated by the endo/sarcoplasmic reticulum Ca2+ sensor stromal interaction molecule 1 (STIM1). There is considerable debate about whether canonical transient receptor potential 1 (TRPC1) proteins also form store-operated channels (SOCs), and if they do, is Orai1 involved. We recently showed that stimulation of TRPC1-based SOCs involves store depletion inducing STIM1-evoked Gαq/PLCβ1 activity in contractile vascular smooth muscle cells (VSMCs). Therefore the present work investigates the role of Orai1 in activation of TRPC1-based SOCs in freshly isolated mesenteric artery VSMCs from wild-type (WT) and Orai1-/- mice. Store-operated whole-cell and single channel currents recorded from WT and Orai1-/- VSMCs had similar properties, with relatively linear current-voltage relationships, reversal potentials of about +20mV, unitary conductances of about 2pS, and inhibition by anti-TRPC1 and anti-STIM1 antibodies. In Orai1-/- VSMCs, store depletion induced PLCβ1 activity measured with the fluorescent phosphatidylinositol 4,5-bisphosphate/inositol 1,4,5-trisphosphate biosensor GFP-PLCδ1-PH, which was prevented by knockdown of STIM1. In addition, in Orai1-/- VSMCs, store depletion induced translocation of STIM1 from within the cell to the plasma membrane where it formed STIM1-TRPC1 interactions at discrete puncta-like sites. These findings indicate that activation of TRPC1-based SOCs through a STIM1-activated PLCβ1 pathway are likely to occur independently of Orai1 proteins, providing evidence that TRPC1 channels form genuine SOCs in VSMCs with a contractile phenotype.
format Artículo
author Shi, Jian
Miralles, Francesc
Kinet, Jean-Pierre
Birnbaumer, Lutz
Large, William A.
Albert, Anthony P.
author_facet Shi, Jian
Miralles, Francesc
Kinet, Jean-Pierre
Birnbaumer, Lutz
Large, William A.
Albert, Anthony P.
author_sort Shi, Jian
title Evidence that Orai1 does not contribute to store-operated TRPC1 channels in vascular smooth muscle cells
title_short Evidence that Orai1 does not contribute to store-operated TRPC1 channels in vascular smooth muscle cells
title_full Evidence that Orai1 does not contribute to store-operated TRPC1 channels in vascular smooth muscle cells
title_fullStr Evidence that Orai1 does not contribute to store-operated TRPC1 channels in vascular smooth muscle cells
title_full_unstemmed Evidence that Orai1 does not contribute to store-operated TRPC1 channels in vascular smooth muscle cells
title_sort evidence that orai1 does not contribute to store-operated trpc1 channels in vascular smooth muscle cells
publisher Taylor & Francis
publishDate 2019
url https://repositorio.uca.edu.ar/handle/123456789/8727
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