ABSTRACT
This chapter focuses on the three subfamilies of transient receptor potential (TRP) channels are recognized as thermoTRPs: TRP ankyrin (TRPA1), transient receptor potential melastatin, TRP melastatin, and TRP vanilloid (TRPV1–4) and discusses these channels and their mechanisms of gating. These key proteins provide the molecular substrate for the detection of temperature and temperature changes, in organisms as varied as worms and humans and play important roles in pain, inflammation, and other physiological processes. A unique mechanism of gating present in thermoTRP channels is activation by covalent modification of intracellular cysteines, which could be considered a ligand-induced mechanism. Several early mutagenesis experiments identified mutations in the pore region that differentially stabilize or disrupt temperature-induced opening in TRPV1, TRPV3, and TRPA1. The role of intracellular regions was first explored in TRPV1 and TRPM8, heat- and cold-activated channels, respectively. An intriguing structural feature of thermoTRPs is the presence of the multiple ankyrin repeats in the N-terminus.
