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 (Corresponding Author), Chih-Cheng Chen (Corresponding Author)

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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 due to substrate deformation-induced neurite stretching, but not to direct neurite indentation. In behavioral 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.
Original languageEnglish
Article number11460
Pages (from-to)1-15
Number of pages15
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 10 May 2016

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