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TRPM8 is a neuronal osmosensor that regulates eye blinking in mice
Talisia Quallo1, Nisha Vastani1, Elisabeth Horridge1
1Wolfson Centre for Age Related Diseases, King's College London, London SE1 1UL, UK.
Nature Communications
|May 23, 2015
Summary
The cold-sensitive TRPM8 channel (transient receptor potential channel, subfamily M, member 8) acts as a peripheral osmosensor. This channel regulates eye-blinking by responding to changes in osmotic pressure.
Area of Science:
- Neuroscience
- Sensory Biology
- Molecular Physiology
Background:
- Peripheral sensory neurons detect environmental stimuli, including osmotic changes.
- The specific molecular mechanisms underlying neuronal responses to osmolality remain largely unidentified.
Purpose of the Study:
- To elucidate the mechanism by which peripheral sensory neurons detect and respond to increased extracellular osmolality.
- To identify the role of the TRPM8 channel in osmosensation and its contribution to physiological responses like eye-blinking.
Main Methods:
- Electrophysiological recordings from mouse dorsal root ganglion (DRG) and trigeminal ganglion (TG) neurons.
- Utilized TRPM8 antagonists and knockout mouse models (Trpm8-/-).
- Investigated TRPM8 channel function in heterologous expression systems and a mouse corneal preparation.
Main Results:
- Increased osmolality excited isolated DRG and TG neurons expressing the TRPM8 channel.
- These hyperosmotic responses were dependent on TRPM8 function, as shown by antagonist blockade and absence in Trpm8(-/-) mice.
- TRPM8 activation by osmolality was confirmed in heterologous systems, and TRPM8-expressing corneal afferent neurons showed osmolality-regulated electrical activity.
Conclusions:
- TRPM8 functions as a critical peripheral osmosensor in sensory neurons.
- TRPM8 plays a significant role in the regulation of normal eye-blinking behavior in mice.
- TRPM8 represents a novel target for modulating responses related to ocular surface sensation and irritation.

