Cold sensing by Na V 1.8-positive and Na V 1.8-negative sensory neurons

• DOI: 10.1073/pnas.1814545116
• Publication Date: 2019-02-12T22:46:11Z
• Authors: A. P. Luiz; D. I. MacDonald; S. Santana-Varela; Q. Millet; S. Sikandar; J. N. Wood; E. C. Emery
• Keywords: TRPM8; Cold sensitivity

The ability to detect environmental cold serves as an important survival tool. sodium channels NaV1.8 and NaV1.9, well the TRP channel Trpm8, have been shown contribute sensation in mice. Surprisingly, transcriptional profiling shows that NaV1.8/NaV1.9 Trpm8 are expressed nonoverlapping neuronal populations. Here we used vivo GCaMP3 imaging identify cold-sensing populations of sensory neurons live We find ∼80% responsive down 1 °C do not express NaV1.8, genetic deletion does affect relative number, distribution, or maximal response cold-sensitive neurons. Furthermore, had no observable effect on transient cold-induced (≥5 °C) behaviors mice, measured by cold-plantar, cold-plate (5 10 °C), acetone tests. In contrast, nocifensive-like behavior extreme stimulation (-5 was completely absent mice lacking NaV1.8. Fluorescence-activated cell sorting (FACS) subsequent microarray analysis activated at 4 identified enriched repertoire ion channels, which include Trp potassium Kcnk9, potentially required for sensing above freezing temperatures mouse DRG These data demonstrate complexity mechanisms neurons, revealing a principal role NaV1.8-negative both innocuous acute noxious cooling °C, while NaV1.8-positive likely responsible transduction prolonged temperatures, where tissue damage causes pan-nociceptor activation.