Submitted on December 26, 2007
Accepted on January 23, 2008
Cutaneous Sensory Neurons Expressing the Mrgprd Receptor Sense Extracellular ATP and are Putative Nociceptors
Gregory Dussor1*, Mark J Zylka2, David J Anderson3, and Edwin W McCleskey1
1 Vollum Institute, Oregon Health & Science University, Portland, Oregon, United States
2 Cell and Molecular Physiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States
3 Division of Biology, California Institute of Technology, Howard Hughes Medical Institute, Pasadena, California, United States
* To whom correspondence should be addressed. E-mail: dussorg{at}email.arizona.edu.
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 non-peptidergic nociceptors. Using patch clamp of dissociated mouse 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++ 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.
