title: Sensory discrimination between innocuous and noxious cold by TRPM8-expressing DRG neurons of rats.
abstract: The TRPM8 channel is a principal cold transducer that is expressed on some primary afferents of the somatic and cranial sensory systems. However, it is uncertain whether TRPM8-expressing afferent neurons have the ability to convey innocuous and noxious cold stimuli with sensory discrimination between the two sub-modalities. Using rat dorsal root ganglion (DRG) neurons and the patch-clamp recording technique, we characterized membrane and action potential properties of TRPM8-expressing DRG neurons at 24°C and 10°C. TRPM8-expressing neurons could be classified into TTX-sensitive (TTXs/TRPM8) and TTX-resistant (TTXr/TRPM8) subtypes based on the sensitivity to tetrodotoxin (TTX) block of their action potentials. These two subtypes of cold-sensing cells displayed different membrane and action potential properties. Voltage-activated inward Na(+) currents were highly susceptible to cooling temperature and abolished by ~95% at 10°C in TTXs/TRPM8 DRG neurons, but remained substantially large at 10°C in TTXr/TRPM8 cells. In both TTXs/TRPM8 and TTXr/TRPM8 cells, voltage-activated outward K(+) currents were substantially inhibited at 10°C, and the cooling-sensitive outward currents resembled A-type K(+) currents. TTXs/TRPM8 neurons and TTXr/TRPM8 neurons were shown to fire action potentials at innocuous and noxious cold temperatures respectively, demonstrating sensory discrimination between innocuous and noxious cold by the two subpopulations of cold-sensing DRG neurons. The effects of cooling temperatures on voltage-gated Na(+) channels and A-type K(+) currents are likely to be contributing factors to sensory discrimination of cold by TTXs/TRPM8 and TTXr/TRPM8 afferent neurons.
authors.affiliation: Department of Anesthesiology and the Graduate Program in Neuroscience, The University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Sarria
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ling
authors.forename: Guang-Yin
authors.initials: GY
authors.lastname: Xu
authors.forename: Jianguo G
authors.initials: JG
authors.lastname: Gu
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003080:Cold Temperature; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D050053:TRPM Cation Channels / Q000378:metabolism*; D013779:Tetrodotoxin / Q000633:toxicity
chemical_list: D050053:TRPM Cation Channels; C498947:Trpm8 protein, rat; D013779:Tetrodotoxin