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.