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.
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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.).
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Freichel, M., Suh, S., Pfeifer, A. et al. Lack of an endothelial store-operated Ca2+ current impairs agonist-dependent vasorelaxation in TRP4−/− mice. Nat Cell Biol 3, 121–127 (2001). https://doi.org/10.1038/35055019
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DOI: https://doi.org/10.1038/35055019
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