title: 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.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, 128 Academia Road, Section 2, Taipei 115, Taiwan.
authors.forename: Shing-Hong
authors.initials: SH
authors.lastname: Lin
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, 128 Academia Road, Section 2, Taipei 115, Taiwan.|Department of Life Science, National Taiwan University, Taipei 106, Taiwan.
authors.forename: Yuan-Ren
authors.initials: YR
authors.lastname: Cheng
authors.affiliation: School of Biological and Biomedical Sciences, University of Durham, Durham DH1 3LE, UK.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Banks
authors.affiliation: Department of Life Science, National Taiwan University, Taipei 106, Taiwan.
authors.forename: Ming-Yuan
authors.initials: MY
authors.lastname: Min
authors.affiliation: School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen AB25 2ZD, UK.
authors.forename: Guy S
authors.initials: GS
authors.lastname: Bewick
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, 128 Academia Road, Section 2, Taipei 115, Taiwan.|Department of Life Science, National Taiwan University, Taipei 106, Taiwan.|Taiwan Mouse Clinic-National Comprehensive Mouse Phenotyping and Drug Testing Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Chen
mesh_terms: D062565:Acid Sensing Ion Channels / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000818:Animals; D005727:Ganglia, Spinal / Q000502:physiology; D055786:Gene Knockout Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009470:Muscle Spindles / Q000294:innervation / Q000502:physiology; D018482:Muscle, Skeletal / Q000294:innervation / Q000502:physiology; D010320:Parvalbumins / Q000378:metabolism; D004856:Postural Balance / Q000502:physiology; D011434:Proprioception / Q000502:physiology; D011984:Sensory Receptor Cells / Q000502:physiology*
chemical_list: C508378:ASIC3 protein, mouse; D062565:Acid Sensing Ion Channels; D010320:Parvalbumins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins