TRPM8 is a neuronal osmosensor that regulates eye blinking in mice

TY - JOUR

T1 - TRPM8 is a neuronal osmosensor that regulates eye blinking in mice

AU - Quallo, Talisia

AU - Vastani, Nisha

AU - Horridge, Elisabeth

AU - Gentry, Clive

AU - Parra, Andres

AU - Moss, Sian

AU - Viana, Felix

AU - Belmonte, Carlos

AU - Andersson, David A

AU - Bevan, Stuart

PY - 2015/5/31

Y1 - 2015/5/31

N2 - 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.

AB - 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.

U2 - 10.1038/ncomms8150

DO - 10.1038/ncomms8150

M3 - Article

SN - 2041-1723

VL - 6

SP - 1

EP - 12

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 7150

ER -