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Published April 2008 | public
Journal Article

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.

Additional Information

© 2008 The American Physiological Society. Submitted 26 December 2007; Accepted in final form 23 January 2008. This work was supported by research grants from the National Institutes of Health to E. W. McCleskey and training grant support from the NIH to G. Dussor. D. J. Anderson is an investigator of the Howard Hughes Medical Institute. The authors thank J. Marsh-Haffner for help genotyping mice and Drs. Mark Connor, Frank Porreca, and Theodore Price for comments on this manuscript.

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