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

Agonist-induced Ca2+ entry into cells by both store-operated channels and c hannels activated independently of Ca2+-store depletion has been described in various cell types. The molecular structures of these channels are unkno wn as is, in most cases, their impact on various cellular functions. Here w e describe a store-operated Ca2+ current in vascular endothelium and show t hat endothelial cells of mice deficient in TRP4 (also known as CCE1) lack t his current. As a consequence, agonist-induced Ca2+ entry and vasorelaxatio n is reduced markedly, showing that TRP4 is an indispensable component of s tore-operated channels in native endothelial cells and that these channels directly provide an Ca2+-entry pathway essentially contributing to the regu lation of blood vessel tone.