Evidence for the involvement of ASIC3 in sensory mechanotransduction in proprioceptors

Shing-Hong Lin, Yuan-Ren Cheng, Robert W. Banks, Ming-Yuan Min, Guy S. Bewick () and Chih-Cheng Chen ()
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Shing-Hong Lin: Institute of Biomedical Sciences
Yuan-Ren Cheng: Institute of Biomedical Sciences
Robert W. Banks: School of Biological and Biomedical Sciences, University of Durham
Ming-Yuan Min: National Taiwan University
Guy S. Bewick: School of Medicine, Medical Sciences and Nutrition, University of Aberdeen
Chih-Cheng Chen: Institute of Biomedical Sciences

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms11460

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