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[https://en.wikipedia.org/wiki/TRPV1 TRPV1] (Vanilloid Transient Receptor Potential Type 1) is a non-selective ion channel which, in response to a stimulus, induces an incoming current of cations, primarily calcium and sodium, which causes depolarization of the cell. It is part of the [https://en.wikipedia.org/wiki/Transient_receptor_potential_channel TRP] (Transient Receptor Potential) superfamily and is the first in a subfamily of vanilloid-sensitive TRP channels / channels: TRPVs. | [https://en.wikipedia.org/wiki/TRPV1 TRPV1] (Vanilloid Transient Receptor Potential Type 1) is a non-selective ion channel which, in response to a stimulus, induces an incoming current of cations, primarily calcium and sodium, which causes depolarization of the cell. It is part of the [https://en.wikipedia.org/wiki/Transient_receptor_potential_channel TRP] (Transient Receptor Potential) superfamily and is the first in a subfamily of vanilloid-sensitive TRP channels / channels: TRPVs. | ||
This receptor is expressed by sensory neurons of the dorsal and trigeminal spinal ganglia.TRPV1 is implicated in [https://en.wikipedia.org/wiki/Nociception nociception], its activation by heat or by chemical substances leads to a painful sensation.<ref> | This receptor is expressed by sensory neurons of the dorsal and trigeminal spinal ganglia.TRPV1 is implicated in [https://en.wikipedia.org/wiki/Nociception nociception], its activation by heat or by chemical substances leads to a painful sensation.<ref name="TRPV1">Wikipedia contributors. (2020b, décembre 21). TRPV1. Wikipedia. https://en.wikipedia.org/wiki/TRPV1 (Consulté le: déc. 28, 2020). [En ligne].</ref> | ||
== Structure of TRPV1 == | == Structure of TRPV1 == | ||
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The N-terminal region has 6 repeats of [https://en.wikipedia.org/wiki/Ankyrin ankyrin].<ref>« Structure of the TRPV1 ion channel determined by electron cryo-microscopy | Nature ».https://www.nature.com/articles/nature12822#Fig3 (consulté le déc. 28, 2020)</ref><ref>G. Smutzer et R. K. Devassy, « Integrating TRPV1 Receptor Function with Capsaicin Psychophysics », Advances in Pharmacological Sciences, janv. 14, 2016</ref> | The N-terminal region has 6 repeats of [https://en.wikipedia.org/wiki/Ankyrin ankyrin].<ref>« Structure of the TRPV1 ion channel determined by electron cryo-microscopy | Nature ».https://www.nature.com/articles/nature12822#Fig3 (consulté le déc. 28, 2020)</ref><ref>G. Smutzer et R. K. Devassy, « Integrating TRPV1 Receptor Function with Capsaicin Psychophysics », Advances in Pharmacological Sciences, janv. 14, 2016</ref> | ||
The transmembrane region is composed of '''six transmembrane a helices''' (S1-S6). S1,S2 and S3 helices contain aromatic side chain (S1 : Y441,Y444,Y555 S2: F488 S3 : F516).<ref>« Structure of the TRPV1 ion channel determined by electron cryo-microscopy | Nature ». https://www.nature.com/articles/nature12822#Fig3 (consulté le déc. 28, 2020)</ref>. A small hydrophobic domain beetween S5 and S6 with a re-entrant loop constitutes the pore allowing the passage of ions through the TRPV1 receptor.<ref | The transmembrane region is composed of '''six transmembrane a helices''' (S1-S6). S1,S2 and S3 helices contain aromatic side chain (S1 : Y441,Y444,Y555 S2: F488 S3 : F516).<ref>« Structure of the TRPV1 ion channel determined by electron cryo-microscopy | Nature ». https://www.nature.com/articles/nature12822#Fig3 (consulté le déc. 28, 2020)</ref>. A small hydrophobic domain beetween S5 and S6 with a re-entrant loop constitutes the pore allowing the passage of ions through the TRPV1 receptor.<ref name="TRPV1"/> | ||
'''Threonin''' residu (T550) and '''tyrosin''' residu (Y511) located on the fifth and the third transmembrane helices are very conserved. Threonin 550 and tyrosin 511 are implicated in TRPV1 activation by [https://en.wikipedia.org/wiki/Vanilloids vanilloids] and in pain sensation.<ref>R. Kumar, A. Hazan, A. Basu, N. Zalcman, H. Matzner, et A. Priel, « Tyrosine Residue in the TRPV1 Vanilloid Binding Pocket Regulates Deactivation Kinetics », J. Biol. Chem., vol. 291, no 26, p. 13855‑13863, juin 2016, doi: 10.1074/jbc.M116.726372.</ref> | '''Threonin''' residu (T550) and '''tyrosin''' residu (Y511) located on the fifth and the third transmembrane helices are very conserved. Threonin 550 and tyrosin 511 are implicated in TRPV1 activation by [https://en.wikipedia.org/wiki/Vanilloids vanilloids] and in pain sensation.<ref>R. Kumar, A. Hazan, A. Basu, N. Zalcman, H. Matzner, et A. Priel, « Tyrosine Residue in the TRPV1 Vanilloid Binding Pocket Regulates Deactivation Kinetics », J. Biol. Chem., vol. 291, no 26, p. 13855‑13863, juin 2016, doi: 10.1074/jbc.M116.726372.</ref> | ||
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The capsaicin cycle binds via hydrogen bounds to amino acids on the S3 helix (Y511, S513), on the S4-S5 linker (E571) and on the S6 helix (T671). The amid group of capsaicin binds the S4 helix (T551).<ref>G. Smutzer et R. K. Devassy, « Integrating TRPV1 Receptor Function with Capsaicin Psychophysics », Advances in Pharmacological Sciences, janv. 14, 2016.</ref> | The capsaicin cycle binds via hydrogen bounds to amino acids on the S3 helix (Y511, S513), on the S4-S5 linker (E571) and on the S6 helix (T671). The amid group of capsaicin binds the S4 helix (T551).<ref>G. Smutzer et R. K. Devassy, « Integrating TRPV1 Receptor Function with Capsaicin Psychophysics », Advances in Pharmacological Sciences, janv. 14, 2016.</ref> | ||
Capsaicin maintains TRPV1 in an open state by «pull and contact» interactions. A conformational change wave spread over the whole pore.<ref>F. Yang et al., « The conformational wave in capsaicin activation of transient receptor potential vanilloid 1 ion channel », Nat. Commun., vol. 9, no 1, Art. no 1, juill. 2018, doi: 10.1038/s41467-018-05339-6.</ref>. This leads to the massive enter of Ca2+ and Na+ in the cytoplasm of the nerve fiber and to the depolarization of the nerve fiber. When depolarization reach a theshold value it triggers the generation of an [https://en.wikipedia.org/wiki/Action_potential action potential] causing a painful sensation.<ref | Capsaicin maintains TRPV1 in an open state by «pull and contact» interactions. A conformational change wave spread over the whole pore.<ref>F. Yang et al., « The conformational wave in capsaicin activation of transient receptor potential vanilloid 1 ion channel », Nat. Commun., vol. 9, no 1, Art. no 1, juill. 2018, doi: 10.1038/s41467-018-05339-6.</ref>. This leads to the massive enter of Ca2+ and Na+ in the cytoplasm of the nerve fiber and to the depolarization of the nerve fiber. When depolarization reach a theshold value it triggers the generation of an [https://en.wikipedia.org/wiki/Action_potential action potential] causing a painful sensation.<ref name="TRPV1"/> | ||
====Resiniferatoxin (RTX)==== | ====Resiniferatoxin (RTX)==== | ||
