TRPV1 channel

Channel name TRPV11,2,3,4,5,6,7,8
Description Vanilloid (capsaicin) receptor and noxious thermosensor
Other names VR1, OTRPC1
Molecular information Human unigene: Hs0.268606, chr. 17p13.3
Mouse unigene: Mm0.278432, chr. 11 B3
Associated subunits Not established
Functional assays Patch-clamp, calcium imaging, knockout mouse
Current Outwardly rectifying nonselective current
Conductance 83pS for heat, 77pS for capsaicin activation measured at positive potentials; Erev in saline solution ∼ 0 mV
Ion selectivity PNa/PCa = 1:9 for capsaicin-activated current, permeability
Ca2+ > Mg2+ > Na+ ∼ K+ ∼ Cs+
PNa/PCa = 1:4 for heat-activated current
Activation Increasing temperature shifts voltage activation to the physiological range of voltages
Inactivation cAMP-dependent protein kinase directly phosphorylates TRPV1 to regulate desensitization
Activators Capsaicin (EC50 = 0.7 μM), resiniferatoxin (EC50 = 40 nM), anandamide, heat (threshold ∼43°C), extracellular protons (indirect sensitization by bradykinin, NGF), ethanol
Blockers Capsazepine, ruthenium red, iodo-resiniferatoxin, BCTC, PIP2
Gating inhibitors None
Radioligands [3H]Resiniferatoxin
Channel distribution Mainly in trigeminal and dorsal root ganglia, also brain, spinal cord
Physiological functions Depolarization and calcium entry in response to heat or endogenous agonist, exogenous capsaicin, pain sensation, vasodilation by anandamide
Mutations and pathophysiology Required for inflammatory thermal hyperalgesia; capsaicin binding site has been determined
Pharmacological significance Potential target for pain-relieving agents
Comments TRPV1 is not activated by store depletion
  • chr., chromosome; NGF, nerve growth factor.

  • 1. Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, and Julius D (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature (Lond) 389:816-824

  • 2. Chuang HH, Prescott ED, Kong H, Shields S, Jordt SE, Basbaum AI, Chao MV, and Julius D (2001) Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition. Nature (Lond) 411:957-962

  • 3. Birder LA, Nakamura Y, Kiss S, Nealen ML, Barrick S, Kanai AJ, Wang E, Ruiz G, De Groat WC, Apodaca G, et al. (2002) Altered urinary bladder function in mice lacking the vanilloid receptor TRPV1. Nat Neurosci 5:856-860

  • 4. Hu HZ, Gu Q, Wang C, Colton CK, Tang J, Kinoshita-Kawada M, Lee LY, Wood JD, and Zhu MX (2004) 2-Aminoethoxydiphenyl borate is a common activator of TRPV1, TRPV2 and TRPV3. J Biol Chem 279:35741-35748

  • 5. Woodbury CJ, Zwick M, Wang S, Lawson JJ, Caterina MJ, Koltzenburg M, Albers KM, Koerber HR, and Davis BM (2004) Nociceptors lacking TRPV1 and TRPV2 have normal heat responses. J Neurosci 24:6410-6415

  • 6. Zhuang ZY, Xu H, Clapham DE, and Ji RR (2004) Phosphatidylinositol 3-kinase activates ERK in primary sensory neurons and mediates inflammatory heat hyperalgesia through TRPV1 sensitization. J Neurosci 24:8300-8309

  • 7. Bhave G, Zhu W, Wang H, Brasier DJ, Oxford GS, and Gereau RW 4th (2002) cAMP-dependent protein kinase regulates desensitization of the capsaicin receptor (VR1) by direct phosphorylation. Neuron 15:721-731

  • 8. Trevisani M, Gazzieri D, Benvenuti F, Campi B, Dinh QT, Groneberg DA, Rigoni M, Emonds-Alt X, Creminon C, Fischer A, et al. (2004) Ethanol causes inflammation in the airways by a neurogenic and TRPV1-dependent mechanism. J Pharmacol Exp Ther 309:1167-1173