Mechanism of temperature-sensing in Transient Receptor Potential channels

Kenton Swartz, Ph.D., Senior Investigator, Molecular Physiology and Biophysics Section, NINDS, NIH The focus of the laboratory is to understand the mechanisms by which ion channel proteins sense critical biological stimuli, including voltage, temperature, chemical ligands and sound. I will give an overview of our program and then focus on our work on Transient Receptor Potential (TRP) channels, a large family of ion channel proteins that are structurally related, yet activated by diverse stimuli, including second messengers, temperature, voltage and natural products such as capsaicin, menthol and tarantula toxins. I will describe our efforts to 1) localize the heat sensors in TRPV1 channels and deduce the mechanism of heat activation, 2) delineate allosteric interactions controlling opening in different TRPV channels and 3) explore the extent to which gating mechanisms are related between different TRP channels. Bae, C., Anselmi, C., Kalia, J., Jara-Oseguera, A., Schwieters, C.D., Krepkiy, D., Lee, C.W., Kim, E.H., Kim, J.I. Faraldo-Gomez, J.D., and Swartz, K.J. (2016) Structural insights into the mechanism of activation of the TRPV1 channel by a membrane-bound tarantula toxin. eLife Feb 10; 5:e11273. PMC4764579 Jara-Oseguera, A., Bae, C. and Swartz, K.J. (2016) An external sodium ion binding site controls temperature-dependent gating in TRPV1 channels. eLife Feb 12; 5:e13356. PMC4764576 Zhang, F., Jara-Oseguera, A., Chang, T.H., Bae, C., Hanson, S.M. and Swartz, K.J. (2018) Heat activation is intrinsic to the pore domain of the TRPV1 channel. Proc.Natl.Acad.Sci. 115, E317-324. PMC5777071