The transient receptor potential family of ion channels

Transient receptor potential (TRP) genes were first described in the fruit fly Drosophila melanogaster. Studies in its visual system identified a visually impaired mutant fly that had a transient response to steady light instead of the sustained electro-retinogram recorded in the wild type [1]. This mutant was therefore called transient receptor potential; however, it took about two decades before the trp gene was identified by Montell and Rubin in 1989 [2]. From its structural resemblance to other cation channels and detailed analysis of the permeation properties of the light-induced current in the trp mutant, the product of the trp gene was proposed to be a six-transmembrane-segment protein that functions as a Ca2+-permeable cation channel [3]. Currently, more than 100 TRP genes have been identified in various animals (Table 1). Human TRP genes are diverse in length and range between 11.4 and about 911 kb, with the number of exons varying from 11 to 39. The overall protein sequence homology between subfamily members in the same species is usually about 35%, but for clear duplication pairs (such as TRPC6 and TRPC7, TRPM4 and TRPM5, and TRPV5 and TRPV6) this may reach 50 to 80%. Regulatory elements in promoters of TRP genes have not been identified.From protein homology, members of the TRP channel family can be seen to fall into seven subfamilies [4]. The number of channels within each subfamily varies across species (Figure 1 and Table 1). The transmembrane segments tend to share the greatest homology within a particular subfamily. The TRPC subfamily ('canonical') comprises closest homologs of Drosophila trp channels. TRPVs ('vanilloid') are named after a founding member vanilloid receptor 1 (now TRPV1). The TRPM subfamily groups homologs of melastatin-1 (now TRPM1). TRPMLs and TRPPs include mucolipins and polycystins, respectively. All members of the TRPA subfamily are nociceptive channels characterized by the presence of about 14 ankyrin repeats. The TRPN subfami