Pentameric TRPV3: an artifact or a clue to channel function?

Transient Receptor Potential (TRP) channels are polymodal cation-permeable ion channels that are activated by a variety of physical and chemical stimuli, including temperature, mechanical stress, pH, and an endless list of natural and synthetic compounds. The ionic currents through activated TRP channels trigger a range of signaling cascades, which create our perception of the environment and guide our reactions to it. The tetrameric assembly of subunits around the central ion-conducting pore has been reported in over 200 structures of more than 20 different TRP channels that belong to seven major subfamilies. Yet, despite this rich knowledge, some aspects of the TRP channel function have remained puzzling and difficult to explain in the context of established structural architecture. One of the debated observations is the phenomenon of pore dilation. For example, prolonged exposure of heterologously expressed TRPV3 to diphenylboronic anhydride (DPBA) or heat caused an abrupt transition from a typical gradually sensitizing TRPV3-mediated current to a current with larger amplitude, lost outward rectification, altered ion selectivity and channel block. Such observations are consistent with the channel pore suddenly becoming wider seconds to minutes after beginning of channel stimulation. The possibility of pore dilation was also suggested for other representatives of temperature-sensitive TRP channels that showed dynamic shifts in ion selectivity.