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Evidence for the involvement of ASIC3 in sensory mechanotransduction in proprioceptors

Lin, Shing-Hong; Cheng, Yuan-Ren; Banks, Robert W.; Min, Ming-Yuan; Bewick, Guy S.; Chen, Chih-Cheng

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Authors

Shing-Hong Lin

Yuan-Ren Cheng

Ming-Yuan Min

Guy S. Bewick

Chih-Cheng Chen



Abstract

Acid-sensing ion channel 3 (ASIC3) is involved in acid nociception, but its possible role in neurosensory mechanotransduction is disputed. We report here the generation of Asic3-knockout/eGFPf-knockin mice and subsequent characterization of heterogeneous expression of ASIC3 in the dorsal root ganglion (DRG). ASIC3 is expressed in parvalbumin (Pv+) proprioceptor axons innervating muscle spindles. We further generate a floxed allele of Asic3 (Asic3f/f) and probe the role of ASIC3 in mechanotransduction in neurite-bearing Pv+ DRG neurons through localized elastic matrix movements and electrophysiology. Targeted knockout of Asic3 disrupts spindle afferent sensitivity to dynamic stimuli and impairs mechanotransduction in Pv+ DRG neurons because of substrate deformation-induced neurite stretching, but not to direct neurite indentation. In behavioural tasks, global knockout (Asic3−/−) and Pv-Cre::Asic3f/f mice produce similar deficits in grid and balance beam walking tasks. We conclude that, at least in mouse, ASIC3 is a molecular determinant contributing to dynamic mechanosensitivity in proprioceptors.

Citation

Lin, S., Cheng, Y., Banks, R. W., Min, M., Bewick, G. S., & Chen, C. (2016). Evidence for the involvement of ASIC3 in sensory mechanotransduction in proprioceptors. Nature Communications, 7, Article 11460. https://doi.org/10.1038/ncomms11460

Journal Article Type Article
Acceptance Date Mar 29, 2016
Online Publication Date May 10, 2016
Publication Date May 10, 2016
Deposit Date Jun 27, 2016
Publicly Available Date Jul 13, 2016
Journal Nature Communications
Publisher Nature Research
Peer Reviewed Peer Reviewed
Volume 7
Article Number 11460
DOI https://doi.org/10.1038/ncomms11460
Public URL https://durham-repository.worktribe.com/output/1380397

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This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/






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