ΠDevelopment/Plasticity/Repair Training-Induced Changes in Brain Morphology

Pleasant cool and unpleasant cold sensations are thought to be mediated by distinct groups of peripheral thermoreceptor neurons that start spiking at different temperatures. The cold-sensitive transient receptor potential channel TRPM8 is present in these neurons, but if and how this channel alone can produce disparate thermal thresholds is not clear. This week, Madrid et al. suggest that slowly inactivating voltage-sensitive potassium channel currents (IKD), which are activated near resting membrane potentials, counteract TRPM8 currents and thereby help determine the temperature threshold in mouse trigeminal ganglion neurons. Cold-sensitive neurons that start spiking at warmer temperatures (31°C) had larger TRPM8-mediated currents and smaller IKD than neurons that started spiking at colder temperatures (24°C). Blocking TRPM8 channels shifted temperature thresholds to colder temperatures, whereas blocking IKD shifted thresholds to warmer temperatures. Moreover, when an IKD blocker was injected into the paw of mice, normally innocuous cool stimuli elicited nociceptive behaviors, suggesting IKD decreases cold sensitivity in vivo.