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Trigeminal Neuralgia TRPM8 Mutation: Enhanced Activation, Basal [Ca2+]i and Menthol Response
Roberta Gualdani1, Jun-Hui Yuan1, Philip R Effraim1
1Institute of Neuroscience (R.G., P.G.), Université catholique de Louvain, B-1200 Brussels, Belgium; Department of Neurology (J.-H.Y., S.D.D.-H., S.G.W.), Yale School of Medicine, New Haven, CT and Center for Neuroscience and Regeneration Research, Veterans Affairs Connecticut Healthcare, West Haven, CT; Department of Anaesthesiology (P.R.E.), Yale School of Medicine New Haven, CT and Center for Neuroscience and Regeneration Research, Veterans Affairs Connecticut Healthcare, West Haven, CT; and Department of Human Neuroscience (G.D.S., A.T., G.C.), Sapienza University, Rome, Italy.
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.
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