Transient receptor potential (TRP) gene superfamily encoding cation channels

The founding member of the transient receptor potential (TRP) protein superfamily was first described in Drosophila. In some of these flies, prolonged exposure to light only induced transient photoreceptor depolarisation, whereas in the wild type the response was sustained. This difference was attributed to mutant trp gene expression. Mammalian TRP homologues have been identified over the past 30 years since the initial trp description in Drosophila. The members of this superfamily constitute a large and very different collection of proteins that are expressed in many tissues and cell types [1]. This superfamily is conserved throughout evolution, from nematodes to humans [2]. They form non-selective monovalent and divalent cation channels with very variable Ca2+/Na+ permeability ratios. Some members are even impermeable for Ca2+, whereas others are highly Ca2+ permeable relative to monovalent cations. TRPV5 and -6 exhibit a Ca2+/Na+ permeability ratio of greater than 100 [3]. This variability is unique by comparison with most other ion channel families. In those cases, the differences in permeation properties within a single family are for the most part very much smaller [4]. TRPs are distinguished from one another based on differences in their primary amino acid sequence rather than ligand affinity or selectivity. This system of classification is used because their properties are heterogeneous and their regulation is complex. The common feature of TRP channels is that they comprise six putative transmembrane spanning domains and a cationpermeable pore formed by a short hydrophobic region between transmembrane domains 5 and 6. They assemble themselves as homo-or heterotetramers to form cation channels (Figure 1). These channels are activated by a remarkable assemblage of very diverse stimuli.Genetic ablation studies in worms, flies and mice indicate that TRPs serve as sensors to elicit responses to a variety of stimuli, ranging from temperature, osmotic pressure, ol