Tissue injury generates endogenous factors that heighten the perception of pain by increasing the response of sensory nerve endings to noxious stimuli. In this process, the capsaicin receptor (TRPV1) is sensitized by phosphatidylinositol-4,5-bisphosphate (PIP2) hydrolysis following phospholipase C activation, but the mechanism that controls capsaicin receptor sensitization has been unclear. In the May 23 Science, Elizabeth Prescott and David Julius of the University of California at San Francisco show that a modular PIP2 binding site is determinant of capsaicin receptor thermal sensitivity (Science, 300:1284-1288, May 23, 2003).
The researchers measured continuous current traces in mutated Xenopus oocytes in response to chemical or thermal stimuli. They observed that mutations in a region of TRPV1 that weaken PIP2–TRPV1 interaction reduce thresholds for chemical or thermal stimuli. Nevertheless, the TRPV1 channels in which this region is replaced with a lipid-binding domain from PIP2-activated potassium channels remain inhibited by PIP2.
"Thus, modification of this ...
