TRPV4 calcium entry channel: a paradigm for gating diversity

Department of Physiology, Campus Gasthuisberg, Katholieke Universiteit Leuven, 3000 Leuven, Belgium The vanilloid receptor-1 (VR1, now TRPV1) was the founding member of a subgroup of cation channels within the TRP family. The TRPV subgroup contains six mammalian members, which all function as Ca 2+ entry channels gated by a variety of physical and chemical stimuli. TRPV4, which displays 45% sequence identity with TRPV1, is characterized by a surprising gating promiscuity: it is activated by hypotonic cell swelling, heat, synthetic 4 -phorbols, and several endogenous substances including arachidonic acid (AA), the endocannabinoids anandamide and 2-AG, and cytochrome P -450 metabolites of AA, such as epoxyeicosatrienoic acids. This review summarizes data on TRPV4 as a paradigm of gating diversity in this subfamily of Ca 2+ entry channels. transient receptor potential; calcium channels; vanilloid receptor Address for reprint requests and other correspondence: B. Nilius, Laboratorium voor Fysiologie, KU Leuven, Campus Gasthuisberg, 3000 Leuven, Belgium (E-mail: Bernd.Nilius{at}med.kuleuven.ac.be ).