Mechanosensitive Channel TRPV4

Abstract

The transient receptor potential vanilloid 4 (TRPV4), a member of the TRP family that has a 6-transmembrane (TM) segment, was first identified as a hypoosmolality-activated Ca2+ permeable channel. The mechanism of opening by hypoosmolality is distinct from direct coupling of membrane tension with conformational changes, such as that which occurs with Msc or TREK, in which phospholipase A2 is sensitive to hypoosmolality and the resulting arachidonic acid metabolites open this channel. TRPV4 is, however, a “multi-micromachine” that senses more diverse physical stimuli and converts them to the Ca2+ signal in various mammalian tissues. Recent analyses suggest that TRPV4 and other molecules together constitute a physiological response, such as cell volume regulation, epithelial permeability, and vascular dilatation. A mouse lacking the TRPV4 gene appeared normal but had unexpected responses to various stimuli; this will provide a clue to elucidate a novel physiological, pathophysiological, and pharmacological significance in the sensation of physical factors.