title: TRPM8 is a neuronal osmosensor that regulates eye blinking in mice.
abstract: Specific peripheral sensory neurons respond to increases in extracellular osmolality but the mechanism responsible for excitation is unknown. Here we show that small increases in osmolality excite isolated mouse dorsal root ganglion (DRG) and trigeminal ganglion (TG) neurons expressing the cold-sensitive TRPM8 channel (transient receptor potential channel, subfamily M, member 8). Hyperosmotic responses were abolished by TRPM8 antagonists, and were absent in DRG and TG neurons isolated from Trpm8(-/-) mice. Heterologously expressed TRPM8 was activated by increased osmolality around physiological levels and inhibited by reduced osmolality. Electrophysiological studies in a mouse corneal preparation demonstrated that osmolality regulated the electrical activity of TRPM8-expressing corneal afferent neurons. Finally, the frequency of eye blinks was reduced in Trpm8(-/-) compared with wild-type mice and topical administration of a TRPM8 antagonist reduced blinking in wild-type mice. Our findings identify TRPM8 as a peripheral osmosensor responsible for the regulation of normal eye-blinking in mice.
authors.affiliation: Wolfson Centre for Age Related Diseases, King's College London, London SE1 1UL, UK.
authors.forename: Talisia
authors.initials: T
authors.lastname: Quallo
authors.affiliation: Wolfson Centre for Age Related Diseases, King's College London, London SE1 1UL, UK.
authors.forename: Nisha
authors.initials: N
authors.lastname: Vastani
authors.affiliation: Wolfson Centre for Age Related Diseases, King's College London, London SE1 1UL, UK.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Horridge
authors.affiliation: Wolfson Centre for Age Related Diseases, King's College London, London SE1 1UL, UK.
authors.forename: Clive
authors.initials: C
authors.lastname: Gentry
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, San Juan de Alicante E-03550, Spain.
authors.forename: Andres
authors.initials: A
authors.lastname: Parra
authors.affiliation: Wolfson Centre for Age Related Diseases, King's College London, London SE1 1UL, UK.
authors.forename: Sian
authors.initials: S
authors.lastname: Moss
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, San Juan de Alicante E-03550, Spain.
authors.forename: Felix
authors.initials: F
authors.lastname: Viana
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, San Juan de Alicante E-03550, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Belmonte
authors.affiliation: Wolfson Centre for Age Related Diseases, King's College London, London SE1 1UL, UK.
authors.forename: David A
authors.identifier: 0000000174518548
authors.initials: DA
authors.lastname: Andersson
authors.affiliation: Wolfson Centre for Age Related Diseases, King's College London, London SE1 1UL, UK.
authors.forename: Stuart
authors.initials: S
authors.lastname: Bevan
mesh_terms: D000200:Action Potentials; D000818:Animals; D001767:Blinking; D016466:CHO Cells; D003080:Cold Temperature; D003315:Cornea / Q000502:physiology; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009994:Osmolar Concentration; D011984:Sensory Receptor Cells / Q000502:physiology*; D050053:TRPM Cation Channels / Q000502:physiology*
chemical_list: D050053:TRPM Cation Channels; C492297:TRPM8 protein, mouse