Activation of Thermosensitive TRP Channels

Abstract

Recently identified thermosensitive transient receptor potential (ThermoTRP) channels are thought to be sensors for ambient temperature. How temperature changes drive activation conformational rearrangement remains unknown. We used electrophysiological methods to investigate temperature-dependent activation of thermoTRP channels as well as the highly temperature-sensitive CLC-0 chloride channel in culture cells. We developed a fast temperature switching technique (20-80°C/sec) to analyze current responses to temperature change.We observed that temperature-driven activation rates of thermoTRP channels were different, while temperature-driven deactivation rates of all the thermoTRP channels were similarly fast. These results indicate that thermoTRP channels can be divided into two groups: fast-activation channels and slow-activation channels. Together with their diverse expression profiles, our results indicate that thermoTRP channels may serve multiple temperature-sensing functions.We also observed that entropic and enthalpic changes associated with temperature-driven activation vary when thermoTRP channels permeate different ions. With previous mutagenesis studies showing that certain residuals in the pore region of TRPV1 and TRPV3 are critical for their temperature-dependent behaviors, our observation further suggests that the pore region is involved in temperature-sensing and gating of thermoTRP channels.View Large Image | View Hi-Res Image | Download PowerPoint Slide