Keratinocytes can modulate and directly initiate nociceptive responses

Mechanical and thermal cues stimulate a specialized group of sensory neurons that terminate in the skin. Three members of the transient receptor potential (TRP) family of channels are expressed in subsets of these neurons and are activated at distinct physiological temperatures. Here, we describe the cloning and characterization of a novel thermosensitive TRP channel. TRPV3 has a unique threshold: It is activated at innocuous (warm) temperatures and shows an increased response at noxious temperatures. TRPV3 is specifically expressed in keratinocytes; hence, skin cells are capable of detecting heat via molecules similar to those in heat-sensing neurons.

Optogenetic silencing strategies using light-driven ion fluxes permit rapid and effective inhibition of neural activity. Using rodent hippocampal neurons we show that silencing activity with a chloride pump can increase the probability of synaptically-evoked spiking in the period following light-activation, whereas this is not the case for a proton pump. This effect can be accounted for by changes to the GABAA receptor reversal potential and demonstrates an important difference between silencing strategies.