Acid potentiation of the capsaicin receptor determined by a key extracellular site

• DOI: 10.1073/pnas.100129497
• Publication Date: 2002-07-26T14:37:36Z
• Authors: Sven-Eric Jordt; Makoto Tominaga; David Julius
• Keywords: Capsaicin; Acid-sensing ion channel

The capsaicin (vanilloid) receptor, VR1, is a sensory neuron-specific ion channel that serves as polymodal detector of pain-producing chemical and physical stimuli. response VR1 to or noxious heat dynamically potentiated by extracellular protons within pH range encountered during tissue acidosis, such associated with arthritis, infarction, tumor growth, other forms injury. A molecular determinant for this important physiological activity was localized an Glu residue (E600) in the region linking fifth transmembrane domain putative pore-forming channel. We suggest key regulatory site receptor setting sensitivity stimuli changes proton concentration. also demonstrate protons, vanilloids, promote opening through distinct pathways, because mutations at second (E648) selectively abrogate proton-evoked activation without diminishing responses Our findings provide evidence stimulus-specific steps offer strategies development novel analgesic agents.