Cl- channel is required for CXCL10-induced neuronal activation and itch response in a murine model of allergic contact dermatitis

Lintao Qu, Kai Fu, Steven G. Shimada, Robert H. Lamotte

Research output: Contribution to journalArticlepeer-review

Abstract

Persistent itch often accompanies allergic contact dermatitis (ACD), but the underlying mechanisms remain largely unexplored. We previously demonstrated that CXCL10/CXCR3 signaling activated a subpopulation of cutaneous primary sensory neurons and mediated itch response after contact hypersensitivity (CHS), a murine model of ACD, induced by squaric acid dibutylester. The purpose of this study was to determine the ionic mechanisms underlying CXCL10-induced neuronal activation and allergic itch. In whole cell recordings, CXCL10 triggered a current in dorsal root ganglion (DRG) neurons innervating the area of CHS. This current was modulated by intracellular Cl- and blocked by the general Cl- channel inhibitors. Moreover, increasing Ca2+ buffering capacity reduced this current. In addition, blockade of Cl- channels significantly suppressed CXCL10-induced Ca2+ response. In behavioral tests, injection of CXCL10 into CHS site exacerbated itch-related scratching behaviors. Moreover, the potentiating behavioral effects of CXCL10 were attenuated by either of two Cl- channel blockers. Thus we suggest that the Cl- channel acts as a downstream target mediating the excitatory and pruritic behavioral effects of CXCL10. Cl- channels may provide a promising therapeutic target for the treatment of allergic itch in which CXCL10/CXCR3 signaling may participate. NEW & NOTEWORTHY The ionic mechanisms underlying CXCL10-induced neuronal activation and allergic itch are largely unexplored. This study revealed that CXCL10 evoked an ionic current mainly carried by Cl- channels. We suggest that Cl- channels are likely key molecular candidates responsible for the CXCL10-evoked neuronal activation and itch-like behaviors in a murine model of allergic contact dermatitis induced by the antigen squaric acid dibutylester. Cl- channels may emerge as a promising drug target for the treatment of allergic itch in which CXCL10/CXCR3 signaling may participate.

Original languageEnglish (US)
Pages (from-to)619-624
Number of pages6
JournalJournal of neurophysiology
Volume118
Issue number1
DOIs
StatePublished - Jul 14 2017

Keywords

  • Allergic contact dermatitis
  • CXCL10
  • CXCR3
  • Cl channel
  • Itch
  • Pain

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

Fingerprint

Dive into the research topics of 'Cl<sup>-</sup> channel is required for CXCL10-induced neuronal activation and itch response in a murine model of allergic contact dermatitis'. Together they form a unique fingerprint.

Cite this