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 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.