Mammalian Transient Receptor Potential (TRP) Cation Channels

Shoichi Irie, Takahisa Furukawa, Irie, Shoichi, Furukawa, Takahisa

The transient receptor potential (TRP) channels play a wide variety of essential roles in the sensory systems of various species, both invertebrates and vertebrates. The TRP channel was first identified as a molecule required for proper light response in Drosophila melanogaster. We and another group recently revealed that TRPM1, the founding member of the melanoma-related transient receptor potential (TRPM) subfamily, is required for the photoresponse in mouse retinal ON-bipolar cells. We further demonstrated that Trpm1 is a component of the transduction cation channel negatively regulated by the metabotropic glutamate receptor 6 (mGulR6) cascade in ON-bipolar cells through a reconstitution experiment using CHO cells expressing Trpm1, mGluR6, and Goα. Furthermore, human TRPM1 mutations are associated with congenital stationary night blindness (CSNB), whose patients lack rod function and suffer from night blindness starting in early childhood. In addition to the function of transduction cation channel, TRPM1 is one of the retinal autoantigens in some paraneoplastic retinopathy (PR) associated with retinal ON-bipolar cell dysfunction. In this chapter, we describe physiological functions of the TRPM1 channel and its underlying biochemical mechanisms in retinal ON-bipolar cells in association with CSNB and PR.