Assembly And Function Of Heteromeric Thermo-sensitive TRP Channels

As one of the improtant sensory system, temperature reception involved sensing temperature changes to avoid the risk from environmental harm and to maintain the stability of the body. For a long time the mechanism of temperature reception has remained vague due to the molecular thermosensor had not been identified. Recently a group of cation channels referred to as ThermoTRPs by molecular cloning has been confirmed as the main cellular temperature sensors. The finding of temperature-sensitive TRP ion channels provides an experimental basis on the study of the mechanisms of temperature sensation on molecular level.Previously we have demonstrated that co-expressing of TRPV1and TRPV3subunits yielded heteromeric channels with intermediate single-channel conductance and gating property. And the assembly between thermo-sensitive TRPV subunits appears to be random.It is generally hypothesized that heteromeric assembly of TRPV channels underlies the molecular basis of fine-tuning of temperature sensation or chemical activation. However, very little is known about the functional properties of the heteromeric channels.In particular, how heteromeric TRPV1/TRPV3channels respond to heat and other stimuli remains unknown. Given the dramatic functional differences between TRPV1and TRPV3homomeric channels, it is of great interest to understand how heteromeric channels formed between them preserve the physiological properties of each subunit type and respond to benign or noxious stimuli.In the present study, we investigated the functional properties of heteromeric TRPV1/TRPV3channel activated by voltage, chemicals and heat. We also extended our study to the assembly of other heteromeric Thermo-sensitive TRP channels.Our results demonstrate that heteromeric TRPV1/TRPV3channels exhibit distinct temperature sensitivity, activation threshold, and heat-induced sensitization. Changes in gating properties apparently originate from interactions between TRPV1and TRPV3subunits. Thus, our results suggest that heteromeric TRPV1/TRPV3channels may serve as polymodal receptor for detecting tempertature changes and chemical irritants, especially noxicious stimuli.They may provide targets of novel therapeutic potentials for fine-tuning heat sensitivity as well as neuronal pain.