TRPC

Abstract: The transient receptor potential (TRP) superfamily consists of a large number of cation channels that are mostly permeable to both monovalent and divalent cations. The 28 mammalian TRP channels can be subdivided into six main subfamilies: the TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPP (polycystin), TRPML (mucolipin), and the TRPA (ankyrin) groups. TRP channels are expressed in almost every tissue and cell type and play an important role in the regulation of various cell functions. Currently, significant scientific effort is being devoted to understanding the physiology of TRP channels and their relationship to human diseases. At this point, only a few channelopathies in which defects in TRP genes are the direct cause of cellular dysfunction have been identified. In addition, mapping of TRP genes to susceptible chromosome regions (e.g., translocations, breakpoint intervals, increased frequency of polymorphisms) has been considered suggestive of the involvement of these channels in hereditary diseases. Moreover, strong indications of the involvement of TRP channels in several diseases come from correlations between levels of channel expression and disease symptoms. Finally, TRP channels are involved in some systemic diseases due to their role as targets for irritants, inflammation products, and xenobiotic toxins. The analysis of transgenic models allows further extrapolations of TRP channel deficiency to human physiology and disease. In this review, we provide an overview of the impact of TRP channels on the pathogenesis of several diseases and identify several TRPs for which a causal pathogenic role might be anticipated.

Abstract: The transient receptor potential (TRP) protein superfamily consists of a diverse group of cation channels that bear structural similarities to Drosophila TRP. TRP channels play important roles in nonexcitable cells; however, an emerging theme is that many TRP-related proteins are expressed predominantly in the nervous system and function in sensory physiology. The TRP superfamily is divided into seven subfamilies, the first of which is composed of the "classical" TRPs" (TRPC subfamily). Some TRPCs may be store-operated channels, whereas others appear to be activated by production of diacylglycerol or regulated through an exocytotic mechanism. Many members of a second subfamily (TRPV) function in sensory physiology and respond to heat, changes in osmolarity, odorants, and mechanical stimuli. Two members of the TRPM family function in sensory perception and three TRPM proteins are chanzymes, which contain C-terminal enzyme domains. The fourth and fifth subfamilies, TRPN and TRPA, include proteins with many ankyrin repeats. TRPN proteins function in mechanotransduction, whereas TRPA1 is activated by noxious cold and is also required for the auditory response. In addition to these five closely related TRP subfamilies, which comprise the Group 1 TRPs, members of the two Group 2 TRP subfamilies, TRPP and TRPML, are distantly related to the group 1 TRPs. Mutations in the founding members of these latter subfamilies are responsible for human diseases. Each of the TRP subfamilies are represented by members in worms and flies, providing the potential for using genetic approaches to characterize the normal functions and activation mechanisms of these channels.