Mammals detect temperature with specialized neurons in the peripheral nervous system. Four TRPV-class channels have been implicated in sensing heat, and one TRPM-class channel in sensing cold. The combined range of temperatures that activate these channels covers a majority of the relevant physiological spectrum sensed by most mammals, with a significant gap in the noxious cold range. Here, we describe the characterization of ANKTM1, a cold-activated channel with a lower activation temperature compared to the cold and menthol receptor, TRPM8. ANKTM1 is a distant family member of TRP channels with very little amino acid similarity to TRPM8. It is found in a subset of nociceptive sensory neurons where it is coexpressed with TRPV1/VR1 (the capsaicin/heat receptor) but not TRPM8. Consistent with the expression of ANKTM1, we identify noxious cold-sensitive sensory neurons that also respond to capsaicin but not to menthol.
Bibliographical noteFunding Information:
We thank Sian Colley, Shelley Halpain, Nancy Hong, Thomas Krucker, Van Lee, Xiaorong Liu, Aziz Moqrich, Matt Petrus, and Jim Watson for valuable contributions and input. Supported in part by grants from the NIH and Novartis. A.P. is a Basil O'Connor and Damon Runyon scholar.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)