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The TRP Superfamily of Cation Channels: Emerging Roles in Epithelial Physiology

APS Epithelia Transport Group
Peter R. Smith
C. Montell, M. Zhu, D. Cohen and M. Hediger

The TRP (transient receptor potential) superfamily of cation channels function in a diversity of physiological processes ranging from temperature and pain perception to cell death.  Although members of the TRP superfamily show significant homology and structural similarities (6 transmembrane domains), they vary dramatically in their ion selectivity and modes of activation.  Remarkably, several members of the superfamily are chanzymes, channels with enzymes linked to the C termini of the ion channel domain.  Based upon a recent unification of the nomenclature, the > 20 members of this novel superfamily are grouped into 3 subfamilies: TRPC, TRPV and TRPM.  Although the TRP channels are best known for their roles in signal transduction in sensory cells and store dependent Ca²⁺ influx in non-excitable cells, the roles for TRP channels in epithelial physiology are rapidly emerging.  TRPV4, which is predominantly expressed in the distal nephron and gated by changes in hypotonicity and cell volume, has been proposed to function as an osmosensor.  TRPV5 and TRPV6 have been identified as epithelial Ca²⁺ channels functioning in intestinal and renal Ca²⁺ reabsorption.  Mutations in TRPM, a chanzyme, have been linked to familial hypomagnesemia with secondary hypocalcemia, an autosomal recessive disease associated with a defect in intestinal and renal Mg²⁺ absorption.

This symposium will provide an overview of the TRP channel superfamily and highlight the emerging roles of these diverse channels in epithelial physiology.