Evidence for the involvement of ASIC3 in sensory mechanotransduction in proprioceptors.

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 (Asic3(f/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::Asic3(f/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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Lin SH,Cheng YR,Banks RW,Min MY,Bewick GS,Chen CC

doi

10.1038/ncomms11460

subject

Has Abstract

pub_date

2016-05-10 00:00:00

pages

11460

issn

2041-1723

pii

ncomms11460

journal_volume

7

pub_type

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