Cutaneous sensory neurons expressing the Mrgprd receptor sense extracellular ATP and are putative nociceptors.
Sensory neurons expressing the Mrgprd receptor are known to innervate the outermost living layer of the epidermis, the stratum granulosum. The sensory modality that these neurons signal and the stimulus that they respond to are not established, although immunocytochemical data suggest they could be nonpeptidergic nociceptors. Using patch clamp of dissociated mouse dorsal root ganglion (DRG) neurons, the present study demonstrates that Mrgprd+ neurons have several properties typical of nociceptors: long-duration action potentials, TTX-resistant Na(+) current, and Ca(2+) currents that are inhibited by mu opioids. Remarkably, Mrgprd+ neurons respond almost exclusively to extracellular ATP with currents similar to homomeric P2X3 receptors. They show little or no sensitivity to other putative nociceptive agonists, including capsaicin, cinnamaldehyde, menthol, pH 6.0, or glutamate. These properties, together with selective innervation of the stratum granulosum, indicate that Mrgprd+ neurons are nociceptors in the outer epidermis and may respond indirectly to external stimuli by detecting ATP release in the skin.
Dussor
G
G
Vollum Institute L474, Oregon Health and Science University, Portland, Oregon, USA. dussorg@email.arizona.edu
Zylka
M J
MJ
Anderson
D J
DJ
McCleskey
E W
EW
D000200:Action Potentials / Q000502:physiology; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D030801:Animals, Genetically Modified; D004594:Electrophysiology; D005110:Extracellular Space / Q000378:metabolism*; D005260:Female; D049452:Green Fluorescent Proteins; D015640:Ion Channel Gating; D051379:Mice; D008810:Mice, Inbred C57BL; D009475:Neurons, Afferent / Q000378:metabolism* / Q000502:physiology*; D009619:Nociceptors / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010641:Phenotype; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis*; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000294:innervation*; D013779:Tetrodotoxin / Q000494:pharmacology
D000779:Anesthetics, Local; C497098:Mrgprd protein, mouse; D043562:Receptors, G-Protein-Coupled; D049452:Green Fluorescent Proteins; D013779:Tetrodotoxin; D000255:Adenosine Triphosphate