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This Article Full Text Full Text (PDF) All Versions of this Article: 99/4/1581    most recent 01396.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Dussor, G. Articles by McCleskey, E. W. PubMed PubMed Citation Articles by Dussor, G. Articles by McCleskey, E. W.

Cutaneous Sensory Neurons Expressing the Mrgprd Receptor Sense Extracellular ATP and Are Putative Nociceptors

¹Vollum Institute L474, Oregon Health and Science University, Portland, Oregon; ²Department of Cell and Molecular Physiology, University of North Carolina Neuroscience Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina; and ³Division of Biology and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California

Submitted 26 December 2007; accepted in final form 23 January 2008

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 Ca²⁺ 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.