Lack of an endothelial store-operated Ca2+ current impairs agonist-dependent vasorelaxation in TRP4-/- mice

Marc Freichel; Suk Hyo Suh; Alexander Pfeifer; Ulli Schweig; Claudia Trost; Petra Weißgerber; Martin Biel; Stephan Philipp; Doris Freise; Guy Droogmans; Franz Hofmann; Veit Flockerzi; Bernd Nilius

doi:10.1038/35055019

Lack of an endothelial store-operated Ca²⁺ current impairs agonist-dependent vasorelaxation in TRP4^-/- mice

Marc Freichel, Suk Hyo Suh, Alexander Pfeifer, Ulli Schweig, Claudia Trost, Petra Weißgerber, Martin Biel, Stephan Philipp, Doris Freise, Guy Droogmans, Franz Hofmann, Veit Flockerzi, Bernd Nilius

Department of Physiology

Research output: Contribution to journal › Article › peer-review

531 Scopus citations

Abstract

Agonist-induced Ca²⁺ entry into cells by both store-operated channels and channels activated independently of Ca²⁺store depletion has been described in various cell types. The molecular structures of these channels are unknown as is, in most cases, their impact on various cellular functions. Here we describe a store-operated Ca²⁺ current in vascular endothelium and show that endothelial cells of mice deficient in TRP4 (also known as CCE1) lack this current. As a consequence, agonist-induced Ca²⁺ entry and vasorelaxation is reduced markedly, showing that TRP4 is an indispensable component of store-operated channels in native endothelial cells and that these channels directly provide an Ca²⁺-entry pathway essentially contributing to the regulation of blood vessel tone.

Original language	English
Pages (from-to)	121-127
Number of pages	7
Journal	Nature Cell Biology
Volume	3
Issue number	2
DOIs	https://doi.org/10.1038/35055019
State	Published - 2001

Bibliographical note

Funding Information:
ACKNOWLEDGEMENTS We thank S. Buchholz, G. Ulrich and J. Prenen for excellent technical support; F. Zimmermann for blastocyst injection and transfer; L. H. Philipson for providing mtrp4 cDNA; and R. Vennekens, M. Hoth and A. Cavalié for helpful discussion. This work was supported by the Deutsche Forschungsgemeinschaft (V.F.); the Belgian Federal Government, the Flemish Government and the Onderzoeksraad KU Leuven (B.N.); the Interuniversity Poles of Attraction Program, the Prime Ministers Office IUAP, “Levenslijn”, and the Fonds der Chemischen Industrie (V.F.). Correspondance and requests for materials should be addressed to V.F. or to B.N.

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10.1038/35055019

Cite this

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title = "Lack of an endothelial store-operated Ca2+ current impairs agonist-dependent vasorelaxation in TRP4-/- mice",

abstract = "Agonist-induced Ca2+ entry into cells by both store-operated channels and channels activated independently of Ca2+store depletion has been described in various cell types. The molecular structures of these channels are unknown as is, in most cases, their impact on various cellular functions. Here we describe a store-operated Ca2+ current in vascular endothelium and show that endothelial cells of mice deficient in TRP4 (also known as CCE1) lack this current. As a consequence, agonist-induced Ca2+ entry and vasorelaxation is reduced markedly, showing that TRP4 is an indispensable component of store-operated channels in native endothelial cells and that these channels directly provide an Ca2+-entry pathway essentially contributing to the regulation of blood vessel tone.",

author = "Marc Freichel and Suh, {Suk Hyo} and Alexander Pfeifer and Ulli Schweig and Claudia Trost and Petra Wei{\ss}gerber and Martin Biel and Stephan Philipp and Doris Freise and Guy Droogmans and Franz Hofmann and Veit Flockerzi and Bernd Nilius",

note = "Funding Information: ACKNOWLEDGEMENTS We thank S. Buchholz, G. Ulrich and J. Prenen for excellent technical support; F. Zimmermann for blastocyst injection and transfer; L. H. Philipson for providing mtrp4 cDNA; and R. Vennekens, M. Hoth and A. Cavali{\'e} for helpful discussion. This work was supported by the Deutsche Forschungsgemeinschaft (V.F.); the Belgian Federal Government, the Flemish Government and the Onderzoeksraad KU Leuven (B.N.); the Interuniversity Poles of Attraction Program, the Prime Ministers Office IUAP, “Levenslijn”, and the Fonds der Chemischen Industrie (V.F.). Correspondance and requests for materials should be addressed to V.F. or to B.N.",

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doi = "10.1038/35055019",

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AU - Freichel, Marc

AU - Suh, Suk Hyo

AU - Pfeifer, Alexander

AU - Schweig, Ulli

AU - Trost, Claudia

AU - Weißgerber, Petra

AU - Biel, Martin

AU - Philipp, Stephan

AU - Freise, Doris

AU - Droogmans, Guy

AU - Hofmann, Franz

AU - Flockerzi, Veit

AU - Nilius, Bernd

N1 - Funding Information: ACKNOWLEDGEMENTS We thank S. Buchholz, G. Ulrich and J. Prenen for excellent technical support; F. Zimmermann for blastocyst injection and transfer; L. H. Philipson for providing mtrp4 cDNA; and R. Vennekens, M. Hoth and A. Cavalié for helpful discussion. This work was supported by the Deutsche Forschungsgemeinschaft (V.F.); the Belgian Federal Government, the Flemish Government and the Onderzoeksraad KU Leuven (B.N.); the Interuniversity Poles of Attraction Program, the Prime Ministers Office IUAP, “Levenslijn”, and the Fonds der Chemischen Industrie (V.F.). Correspondance and requests for materials should be addressed to V.F. or to B.N.

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