Heteromeric Heat-Sensitive TRP Channels Exhibit Distinct Temperature and Chemical Response

TRPV1 and TRPV3 are two heat-sensitive channels activated at distinct temperature ranges perceived by human as hot and warm, respectively. Compounds eliciting human sensations of heat or warmth can also potently activate them. While in rodents TRPV3 is expressed predominantly in keratinocytes, in humans TRPV1 and TRPV3 are co-expressed in sensory neurons of dorsal root ganglia and trigeminal ganglion and are known to form heteromeric channels with distinct single-channel conductances as well as sensitivities to TRPV1 activator and inhibitor. However, how heteromeric TRPV1/TRPV3 channels respond to heat and other stimuli remains unknown. In the present study, we examined the behavior of heteromeric TRPV1/TRPV3 channels activated by heat, capsaicin and voltage. Our results demonstrate that the heteromeric channels exhibit distinct temperature sensitivity, activation threshold, and heat-induced sensitization. Changes in gating properties apparently originate from interactions between TRPV1 and TRPV3 subunits. Furthermore, biochemical study demonstrated interactions between the intracellular C termini of TRPV1 and TRPV3, indicating that the recently identified tetrameric assembly domain for homomeric channels also mediates heteromeric subunit assembly. Together, our results suggest that heteromeric TRPV1/TRPV3 channels may contribute to the fine tuning of sensitivity to sensory inputs and pain.View Large Image | View Hi-Res Image | Download PowerPoint Slide