Specificity of cold thermotransduction is determined by differential ionic channel expression.
Sensations of cold are mediated by specific thermoreceptor nerve endings excited by low temperature and menthol. Here we identify a population of cold-sensitive cultured mouse trigeminal ganglion neurons with a unique set of biophysical properties. Their impulse activity during cooling and menthol application was similar to that of cold thermoreceptor fibers in vivo. We show that cooling closes a background K+ channel, causing depolarization and firing that is limited by the slower reduction of a cationic inward current (Ih). In cold-insensitive neurons, firing is prevented by a slow, transient, 4-AP-sensitive K+ current (IKD) that acts as an excitability brake. In addition, pharmacological blockade of IKD induced thermosensitivity in cold-insensitive neurons, a finding that may explain cold allodynia in neuropathic pain. These results suggest that cold sensitivity is not associated to a specific transduction molecule but instead results from a favorable blend of ionic channels expressed in a small subset of sensory neurons.
Viana
Félix
F
Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, Apartado 18, San Juan de Alicante 03550, Spain. felix.viana@umh.es
de la Peña
Elvira
E
Belmonte
Carlos
C
D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003080:Cold Temperature; D008610:Menthol / Q000494:pharmacology; D051379:Mice; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013823:Thermoreceptors / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013697:Thermosensing / Q000502:physiology*; D012668:Trigeminal Ganglion / Q000166:cytology / Q000378:metabolism
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D008610:Menthol; D015761:4-Aminopyridine; D002118:Calcium