Capsaicin, the main pungent ingredient in 'hot' chili peppers, elicits burning pain by activating specific (vanilloid) receptors on sensory nerve endings. We have isolated a functional cDNA encoding a capsaicin receptor from sensory neurons using an expression cloning strategy. The cloned vanilloid receptor (VR1) is a nonselective cation channel with six transmembrane domains that is structurally related to a member of the TRP family. VR1 is also activated by increases in temperature in the nonoxious range (>43 °C. We also find that protons decrease the temperature threshold for VR1 activation such that even moderately acidic conditions (pH<5.9) activate VR1 at room temperature. Analysis of single-channel currents in excised membrane patches suggests that heat or proton gates VR1 directly. VR1 can therefore be viewed as a molecular integrator of chemical and physical stimuli that elicit pain.
