The TRPV4 channel: structure-function relationship and promiscuous gating behaviour

Transient receptor potential (TRP) channels provide an enormous variability of Ca2+ influx mechanisms triggered by a wide range of stimuli. In this review, we discuss the activation properties of the Ca2+- and Mg2+-permeable TRP channel of the vanilloid subfamily TRPV4. This channel is activated by various physical and chemical stimuli, such as cell swelling, heat, phorbols and, probably, by endogenous ligands, which are able to induce Ca2+ entry. Not much is known about the regulation of this channel. We will refer only to a mechanism of Ca2+-dependent inhibition of TRPV4. Possible functional roles of this channel will be correlated with its observed expression pattern. Finally, we discuss the structural determinants of TRPV4 channel function.