Specificity of cold thermotransduction is determined by differential ionic channel expression

Abstract

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 (I_h). In cold-insensitive neurons, firing is prevented by a slow, transient, 4-AP-sensitive K⁺ current (IK_D) that acts as an excitability brake. In addition, pharmacological blockade of IK_D 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.