title: Ocular surface wetness is regulated by TRPM8-dependent cold thermoreceptors of the cornea.
abstract: Basal tearing is crucial to maintaining ocular surface wetness. Corneal cold thermoreceptors sense small oscillations in ambient temperature and change their discharge accordingly. Deletion of the cold-transducing ion channel Transient receptor potential cation channel subfamily M member 8 (TRPM8) in mice abrogates cold responsiveness and reduces basal tearing without affecting nociceptor-mediated irritative tearing. Warming of the cornea in humans also decreases tearing rate. These findings indicate that TRPM8-dependent impulse activity in corneal cold receptors contributes to regulating basal tear flow.
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas, San Juan de Alicante, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Parra
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Madrid
authors.forename: Diego
authors.initials: D
authors.lastname: Echevarria
authors.forename: Susana
authors.initials: S
authors.lastname: del Olmo
authors.forename: Cruz
authors.initials: C
authors.lastname: Morenilla-Palao
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Acosta
authors.forename: Juana
authors.initials: J
authors.lastname: Gallar
authors.forename: Ajay
authors.initials: A
authors.lastname: Dhaka
authors.forename: Félix
authors.initials: F
authors.lastname: Viana
authors.forename: Carlos
authors.initials: C
authors.lastname: Belmonte
mesh_terms: D015761:4-Aminopyridine / Q000378:metabolism; D000818:Animals; D003080:Cold Temperature; D003315:Cornea / Q000378:metabolism*; D015352:Dry Eye Syndromes / Q000209:etiology* / Q000378:metabolism; D008610:Menthol / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009799:Ocular Physiological Phenomena; D011719:Pyrazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051637:Shaker Superfamily of Potassium Channels / Q000378:metabolism; D000074025:TRPA1 Cation Channel; D050053:TRPM Cation Channels / Q000378:metabolism*; D013666:Tears / Q000502:physiology*; D013823:Thermoreceptors / Q000378:metabolism*; D050051:Transient Receptor Potential Channels / Q000235:genetics
chemical_list: C475772:N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carboxamide; D011719:Pyrazines; D011725:Pyridines; D051637:Shaker Superfamily of Potassium Channels; D000074025:TRPA1 Cation Channel; D050053:TRPM Cation Channels; C492297:TRPM8 protein, mouse; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D008610:Menthol; D015761:4-Aminopyridine