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Mrgprd Enhances Excitability in Specific Populations of Cutaneous Murine Polymodal Nociceptors

Rau, Kristofer K. and McIlwrath, Sabrina L. and Wang, Hong and Lawson, JeffreyJ. and Jankowski, Michael P. and Zylka, Mark J. and Anderson, David J. and Koerber, H. Richard (2009) Mrgprd Enhances Excitability in Specific Populations of Cutaneous Murine Polymodal Nociceptors. Journal of Neuroscience, 29 (26). pp. 8612-8619. ISSN 0270-6474. http://resolver.caltech.edu/CaltechAUTHORS:20090908-094020207

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Abstract

The Mas-related G protein-coupled receptor D (Mrgprd) is selectively expressed in nonpeptidergic nociceptors that innervate the outer layers of mammalian skin. The function of Mrgprd in nociceptive neurons and the physiologically relevant somatosensory stimuli that activate Mrgprd^-expressing (Mrgprd^+) neurons are currently unknown. To address these issues, we studied three Mrgprd knock-in mouse lines using an ex vivo somatosensory preparation to examine the role of the Mrgprd receptor and Mrgprd+ afferents in cutaneous somatosensation. In mouse hairy skin, Mrgprd, as marked by expression of green fluorescent protein reporters, was expressed predominantly in the population of nonpeptidergic, TRPV1-negative, C-polymodal nociceptors. In mice lacking Mrgprd, this population of nociceptors exhibited decreased sensitivity to cold, heat, and mechanical stimuli. Additionally, in vitro patch-clamp studies were performed on cultured dorsal root ganglion neurons from Mrgprd^(–/–) and Mrgprd^(+/–) mice. These studies revealed a higher rheobase in neurons from Mrgprd^(–/–) mice than from Mrgprd^(+/–) mice. Furthermore, the application of the Mrgprd ligand β-alanine significantly reduced the rheobase and increased the firing rate in neurons from Mrgprd^(+/–) mice but was without effect in neurons from Mrgprd^(–/–) mice. Our results demonstrate that Mrgprd influences the excitability of polymodal nonpeptidergic nociceptors to mechanical and thermal stimuli.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1523/JNEUROSCI.1057-09.2009DOIUNSPECIFIED
http://www.jneurosci.org/cgi/content/abstract/29/26/8612PublisherUNSPECIFIED
Additional Information:Copyright © 2009 Society for Neuroscience. Received March 4, 2009; revised April 28, 2009; accepted May 18, 2009. This work was supported by National Institutes of Health Grants R01 NS23275 and NS052848 (H.R.K) and P01 NS048499-05 (D.J.A.) and the Sloan Foundation, the Searle Scholars Program, the Klingenstein Foundation, the Whitehall Foundation, the Rita Allen Foundation, and National Institute of Neurological Disorders and Stroke Grant R01 NS060725 (all to M.J.Z.). M.J.Z. is a Rita Allen Foundation Milton E. Cassel Scholar. We sincerely thank Collene Anderson and Weiwen Wang for their excellent technical assistance and Liching Lo for assistance in making the Mrgprd-CRE knock-in mouse.
Funders:
Funding AgencyGrant Number
NIHR01 NS23275
NIHNS052848
NIHP01 NS048499-05
Alfred P. Sloan FoundationUNSPECIFIED
Searle Scholars ProgramUNSPECIFIED
Klingenstein FoundationUNSPECIFIED
Whitehall FoundationUNSPECIFIED
Rita Allen FoundationUNSPECIFIED
National Institute of Neurological Disorders and StrokeR01 NS060725
Howard Hughes Medical InstituteUNSPECIFIED
Record Number:CaltechAUTHORS:20090908-094020207
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20090908-094020207
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:15667
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:08 Sep 2009 17:34
Last Modified:27 Feb 2015 00:09

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