ASIC3 Mediates Itch Sensation in Response to Coincident Stimulation by Acid and Nonproton Ligand.

Zhong Peng, Wei-Guang Li, Chen Huang, Yi-Ming Jiang, Xiang Wang, Michael Xi Zhu, Xiaoyang Cheng, Tian-Le Xu

Cell reports 2015 Oct 13

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The regulation and mechanisms underlying itch sensation are complex. Here, we report a role for acid-sensing ion channel 3 (ASIC3) in mediating itch evoked by certain pruritogens during tissue acidosis. Co-administration of acid with Ser-Leu-Ile-Gly-Arg-Leu-NH2 (SL-NH2) increased scratching behavior in wild-type, but not ASIC3-null, mice, implicating the channel in coincident detection of acidosis and pruritogens. Mechanistically, SL-NH2 slowed desensitization of proton-evoked currents by targeting the previously identified nonproton ligand-sensing domain located in the extracellular region of ASIC3 channels in primary sensory neurons. Ablation of the ASIC3 gene reduced dry-skin-induced scratching behavior and pathological changes under conditions with concomitant inflammation. Taken together, our data suggest that ASIC3 mediates itch sensation via coincident detection of acidosis and nonproton ligands that act at the nonproton ligand-sensing domain of the channel. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Zhong Peng, Wei-Guang Li, Chen Huang, Yi-Ming Jiang, Xiang Wang, Michael Xi Zhu, Xiaoyang Cheng, Tian-Le Xu. ASIC3 Mediates Itch Sensation in Response to Coincident Stimulation by Acid and Nonproton Ligand. Cell reports. 2015 Oct 13;13(2):387-98