Abstract
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 Ca2+ imaging and whole-cell patch-clamp recording.
Results The TRPM8 mutation enhances channel activation, increases basal current amplitude and intracellular [Ca2+] 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.
Glossary
- DMEM=
- Dulbecco's Modified Eagle's Medium;
- EGTA=
- ethylene glycol tetraacetic acid;
- FBS=
- fetal bovine serum;
- GFP=
- green fluorescent protein;
- HEPES=
- 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid;
- HEK=
- human embryonic kidney;
- TN=
- trigeminal neuralgia;
- TRPM8=
- transient Receptor Potential Melastatin 8
Footnotes
Go to Neurology.org/NG for full disclosures. Funding information is provided at the end of the article.
↵* Contributed equally.
The Article Processing Charge was funded by the authors.
- Received August 11, 2020.
- Accepted in final form November 9, 2020.
- Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), 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.
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