Roles for TRPV4 in disease: A discussion of possible mechanisms

Abstract

The transient receptor potential vanilloid 4 (TRPV4) ion channel is a ubiquitously expressed Ca²⁺-permeable ion channel that controls intracellular calcium ([Ca²⁺]_i) homeostasis in various types of cells. The physiological roles for TRPV4 are tissue specific and the mechanisms behind this specificity remain mostly unclarified. It is noteworthy that mutations in the TRPV4 channel have been associated to a broad spectrum of congenital diseases, with most of these mutations mainly resulting in gain-of-function. Mutations have been identified in human patients showing a variety of phenotypes and symptoms, mostly related to skeletal and neuromuscular disorders. Since TRPV4 is so widely expressed throughout the body, it comes as no surprise that the literature is growing in evidence linking this protein to malfunction in systems other than the skeletal and neuromuscular. In this review, we summarize the expression patterns of TRPV4 in several tissues and highlight findings of recent studies that address critical structural and functional features of this channel, particularly focusing on its interactions and signaling pathways related to Ca²⁺ entry. Moreover, we discuss the roles of TRPV4 mutations in some diseases and pinpoint some of the mechanisms underlying pathological states where TRPV4’s malfunction is prominent.