Trigeminal Neuralgia TRPM8 Mutation: Enhanced Activation, Basal [Ca(2+)](i) and Menthol Response

OBJECTIVE: To assess the functional effects of a variant, c.89 G > A (p.Arg30Gln), in the transient receptor potential melastatin 8 (TRPM8) cold-sensing, nonselective cation channel, which we have previously identified in a patient with familial trigeminal neuralgia. METHODS: We carried out Ca(2+...

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Autores principales: Gualdani, Roberta, Yuan, Jun-Hui, Effraim, Philip R., Di Stefano, Giulia, Truini, Andrea, Cruccu, Giorgio, Dib-Hajj, Sulayman D., Gailly, Philippe, Waxman, Stephen G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105906/
https://www.ncbi.nlm.nih.gov/pubmed/33977138
http://dx.doi.org/10.1212/NXG.0000000000000550
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author Gualdani, Roberta
Yuan, Jun-Hui
Effraim, Philip R.
Di Stefano, Giulia
Truini, Andrea
Cruccu, Giorgio
Dib-Hajj, Sulayman D.
Gailly, Philippe
Waxman, Stephen G.
author_facet Gualdani, Roberta
Yuan, Jun-Hui
Effraim, Philip R.
Di Stefano, Giulia
Truini, Andrea
Cruccu, Giorgio
Dib-Hajj, Sulayman D.
Gailly, Philippe
Waxman, Stephen G.
author_sort Gualdani, Roberta
collection PubMed
description OBJECTIVE: To assess the functional effects of a variant, c.89 G > A (p.Arg30Gln), in the transient receptor potential melastatin 8 (TRPM8) cold-sensing, nonselective cation channel, which we have previously identified in a patient with familial trigeminal neuralgia. METHODS: We carried out Ca(2+) imaging and whole-cell patch-clamp recording. RESULTS: The TRPM8 mutation enhances channel activation, increases basal current amplitude and intracellular [Ca(2+)] in cells carrying the mutant channel, and enhances the response to menthol. CONCLUSIONS: We propose that Arg30Gln confers gain-of-function attributes on TRPM8, which contribute to pathogenesis of trigeminal neuralgia in patients carrying this mutation.
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spelling pubmed-81059062021-05-10 Trigeminal Neuralgia TRPM8 Mutation: Enhanced Activation, Basal [Ca(2+)](i) and Menthol Response Gualdani, Roberta Yuan, Jun-Hui Effraim, Philip R. Di Stefano, Giulia Truini, Andrea Cruccu, Giorgio Dib-Hajj, Sulayman D. Gailly, Philippe Waxman, Stephen G. Neurol Genet Article OBJECTIVE: To assess the functional effects of a variant, c.89 G > A (p.Arg30Gln), in the transient receptor potential melastatin 8 (TRPM8) cold-sensing, nonselective cation channel, which we have previously identified in a patient with familial trigeminal neuralgia. METHODS: We carried out Ca(2+) imaging and whole-cell patch-clamp recording. RESULTS: The TRPM8 mutation enhances channel activation, increases basal current amplitude and intracellular [Ca(2+)] in cells carrying the mutant channel, and enhances the response to menthol. CONCLUSIONS: We propose that Arg30Gln confers gain-of-function attributes on TRPM8, which contribute to pathogenesis of trigeminal neuralgia in patients carrying this mutation. Wolters Kluwer 2021-01-11 /pmc/articles/PMC8105906/ /pubmed/33977138 http://dx.doi.org/10.1212/NXG.0000000000000550 Text en Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Article
Gualdani, Roberta
Yuan, Jun-Hui
Effraim, Philip R.
Di Stefano, Giulia
Truini, Andrea
Cruccu, Giorgio
Dib-Hajj, Sulayman D.
Gailly, Philippe
Waxman, Stephen G.
Trigeminal Neuralgia TRPM8 Mutation: Enhanced Activation, Basal [Ca(2+)](i) and Menthol Response
title Trigeminal Neuralgia TRPM8 Mutation: Enhanced Activation, Basal [Ca(2+)](i) and Menthol Response
title_full Trigeminal Neuralgia TRPM8 Mutation: Enhanced Activation, Basal [Ca(2+)](i) and Menthol Response
title_fullStr Trigeminal Neuralgia TRPM8 Mutation: Enhanced Activation, Basal [Ca(2+)](i) and Menthol Response
title_full_unstemmed Trigeminal Neuralgia TRPM8 Mutation: Enhanced Activation, Basal [Ca(2+)](i) and Menthol Response
title_short Trigeminal Neuralgia TRPM8 Mutation: Enhanced Activation, Basal [Ca(2+)](i) and Menthol Response
title_sort trigeminal neuralgia trpm8 mutation: enhanced activation, basal [ca(2+)](i) and menthol response
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105906/
https://www.ncbi.nlm.nih.gov/pubmed/33977138
http://dx.doi.org/10.1212/NXG.0000000000000550
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