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

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