Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
2000 Dec 05;9725:13889-94. doi: 10.1073/pnas.230146497.
Show Gene links
Show Anatomy links
The activation mechanism of rat vanilloid receptor 1 by capsaicin involves the pore domain and differs from the activation by either acid or heat.
Welch JM
,
Simon SA
,
Reinhart PH
.
???displayArticle.abstract???
The recently cloned rat vanilloid receptor, VR1, can be activated by capsaicin, acid, and heat. To determine the molecular mechanisms facilitating channel opening in response to these stimuli, VR1 and six channels containing charge neutralization point mutations surrounding the putative channel pore domain were expressed and characterized in Xenopus laevis oocytes. Steady-state dose-response relationships, current-voltage relationships, ionic selectivities, and single-channel properties were recorded using voltage-clamp techniques. Three of the mutant channels are significantly more sensitive to capsaicin than is wild-type VR1, whereas none differed in their activation by acidic pH or temperature. Furthermore, one of the mutants has lost all positive cooperativity for capsaicin activation (Hill coefficient congruent with 1, VR1 congruent with 2), is much more selective for Ca(2+), and exhibits a lower efficacy for acid than for capsaicin activation. Single-channel recordings show that capsaicin- and acid-activated channels have the same conductance, that the three mutants with increased capsaicin sensitivity exhibit higher open probabilities at submaximal capsaicin concentrations, and that the gating properties of capsaicin activation differ from those of acid activation. These data indicate that VR1 undergoes conformational changes upon capsaicin binding that it does not undergo in response to activation by protons or thermal stimuli. Furthermore, these structural rearrangements include the putative pore domain and reveal the location of an intracellular domain that contributes to the positive cooperativity seen for capsaicin activation.
Bevan,
Sensory neuron-specific actions of capsaicin: mechanisms and applications.
1990, Pubmed
Bevan,
Sensory neuron-specific actions of capsaicin: mechanisms and applications.
1990,
Pubmed
Caterina,
The capsaicin receptor: a heat-activated ion channel in the pain pathway.
1997,
Pubmed
,
Xenbase
Caterina,
A capsaicin-receptor homologue with a high threshold for noxious heat.
1999,
Pubmed
,
Xenbase
Caterina,
Impaired nociception and pain sensation in mice lacking the capsaicin receptor.
2000,
Pubmed
DiChiara,
Distinct effects of Ca2+ and voltage on the activation and deactivation of cloned Ca(2+)-activated K+ channels.
1995,
Pubmed
,
Xenbase
Guenther,
Rises in [Ca2+]i mediate capsaicin- and proton-induced heat sensitization of rat primary nociceptive neurons.
1999,
Pubmed
Gunthorpe,
Voltage- and time-dependent properties of the recombinant rat vanilloid receptor (rVR1).
2000,
Pubmed
Hamill,
Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
1981,
Pubmed
Jordt,
Acid potentiation of the capsaicin receptor determined by a key extracellular site.
2000,
Pubmed
Jung,
Capsaicin binds to the intracellular domain of the capsaicin-activated ion channel.
1999,
Pubmed
Kress,
Capsaicin, protons and heat: new excitement about nociceptors.
1999,
Pubmed
Liu,
Capsaicin, acid and heat-evoked currents in rat trigeminal ganglion neurons: relationship to functional VR1 receptors.
2000,
Pubmed
Lopshire,
The cAMP transduction cascade mediates the prostaglandin E2 enhancement of the capsaicin-elicited current in rat sensory neurons: whole-cell and single-channel studies.
1998,
Pubmed
Morrill,
Isolation of a single carboxyl-carboxylate proton binding site in the pore of a cyclic nucleotide-gated channel.
1999,
Pubmed
,
Xenbase
Nagy,
Noxious heat activates all capsaicin-sensitive and also a sub-population of capsaicin-insensitive dorsal root ganglion neurons.
1999,
Pubmed
Nagy,
Similarities and differences between the responses of rat sensory neurons to noxious heat and capsaicin.
1999,
Pubmed
Perozo,
Structural rearrangements underlying K+-channel activation gating.
1999,
Pubmed
Szallasi,
Vanilloid (Capsaicin) receptors and mechanisms.
1999,
Pubmed
Séguéla,
Molecular cloning, functional properties, and distribution of rat brain alpha 7: a nicotinic cation channel highly permeable to calcium.
1993,
Pubmed
,
Xenbase
Tominaga,
The cloned capsaicin receptor integrates multiple pain-producing stimuli.
1998,
Pubmed
,
Xenbase
Treede,
Evidence for two different heat transduction mechanisms in nociceptive primary afferents innervating monkey skin.
1995,
Pubmed
Vyklický,
Temperature coefficient of membrane currents induced by noxious heat in sensory neurones in the rat.
1999,
Pubmed
Zygmunt,
Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide.
1999,
Pubmed
,
Xenbase
