David Julius Used Capsaicin and Menthol Probes to Identify the TRPV1 and TRPM8 Temperature Sensors

David Julius identified the capsaicin receptor TRPV1, the first cloned vanilloid receptor, using capsaicin as a probe with cDNA library screening and calcium imaging, and confirmed with patch clamp that it is an ion channel mediating Na+/Ca2+ influx that also responds to heat at the human threshold between warmth and burning pain. Using menthol as a probe, he then identified the TRPM8 cold receptor, which opens below about 26 degrees Celsius; TRPM8 knockout mice could not distinguish 20 degree from 30 degree platforms, validating TRP channels as key molecular detectors of environmental temperature. These channels are now targets for developing new analgesics.