RT Journal Article
SR Electronic
T1 Trigeminal Neuralgia TRPM8 Mutation
JF Neurology Genetics
JO Neurol Genet
FD Lippincott Williams & Wilkins
SP e550
DO 10.1212/NXG.0000000000000550
VO 7
IS 1
A1 Gualdani, Roberta
A1 Yuan, Jun-Hui
A1 Effraim, Philip R.
A1 Di Stefano, Giulia
A1 Truini, Andrea
A1 Cruccu, Giorgio
A1 Dib-Hajj, Sulayman D.
A1 Gailly, Philippe
A1 Waxman, Stephen G.
YR 2021
UL http://ng.neurology.org/content/7/1/e550.abstract
AB 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.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