Simultaneous disruption of mouse ASIC1a, ASIC2 and ASIC3 genes enhances cutaneous mechanosensitivity

Sinyoung Kang; Jun Ho Jang; Margaret P Price; Mamta Gautam; Christopher J Benson; Huiyu Gong; Michael J Welsh; Timothy J Brennan

doi:10.1371/journal.pone.0035225

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Simultaneous disruption of mouse ASIC1a, ASIC2 and ASIC3 genes enhances cutaneous mechanosensitivity

Journal article

Open access

Peer reviewed

Simultaneous disruption of mouse ASIC1a, ASIC2 and ASIC3 genes enhances cutaneous mechanosensitivity

Sinyoung Kang, Jun Ho Jang, Margaret P Price, Mamta Gautam, Christopher J Benson, Huiyu Gong, Michael J Welsh and Timothy J Brennan

PloS one, Vol.7(4), pp.e35225-e35225

2012

DOI: 10.1371/journal.pone.0035225

PMCID: PMC3323639

PMID: 22506072

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Abstract

Three observations have suggested that acid-sensing ion channels (ASICs) might be mammalian cutaneous mechanoreceptors; they are structurally related to Caenorhabditis elegans mechanoreceptors, they are localized in specialized cutaneous mechanosensory structures, and mechanical displacement generates an ASIC-dependent depolarization in some neurons. However, previous studies of mice bearing a single disrupted ASIC gene showed only subtle or no alterations in cutaneous mechanosensitivity. Because functional redundancy of ASIC subunits might explain limited phenotypic alterations, we hypothesized that disrupting multiple ASIC genes would markedly impair cutaneous mechanosensation. We found the opposite. In behavioral studies, mice with simultaneous disruptions of ASIC1a, -2 and -3 genes (triple-knockouts, TKOs) showed increased paw withdrawal frequencies when mechanically stimulated with von Frey filaments. Moreover, in single-fiber nerve recordings of cutaneous afferents, mechanical stimulation generated enhanced activity in A-mechanonociceptors of ASIC TKOs compared to wild-type mice. Responses of all other fiber types did not differ between the two genotypes. These data indicate that ASIC subunits influence cutaneous mechanosensitivity. However, it is unlikely that ASICs directly transduce mechanical stimuli. We speculate that physical and/or functional association of ASICs with other components of the mechanosensory transduction apparatus contributes to normal cutaneous mechanosensation.

Acid Sensing Ion Channels

Mice, Inbred C57BL

Mechanoreceptors - physiology

Stress, Mechanical

Behavior, Animal - physiology

Male

Mechanotransduction, Cellular - physiology

Acids - metabolism

Nerve Tissue Proteins - genetics

Mice, Knockout

Animals

Female

Mice

Sodium Channels - genetics

Mechanoreceptors - metabolism

Mechanotransduction, Cellular - genetics

Details

Title: Subtitle: Simultaneous disruption of mouse ASIC1a, ASIC2 and ASIC3 genes enhances cutaneous mechanosensitivity
Creators: Sinyoung Kang - Department of Anesthesia, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America
Jun Ho Jang
Margaret P Price
Mamta Gautam
Christopher J Benson
Huiyu Gong
Michael J Welsh
Timothy J Brennan
Resource Type: Journal article
Publication Details: PloS one, Vol.7(4), pp.e35225-e35225
DOI: 10.1371/journal.pone.0035225
PMID: 22506072
PMCID: PMC3323639
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; United States
Grant note: R01 GM067762 / NIGMS NIH HHS GM067762 / NIGMS NIH HHS Howard Hughes Medical Institute
Language: English
Date published: 2012
Academic Unit: Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Stead Family Department of Pediatrics; Cardiovascular Medicine; Anesthesia; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Neurosurgery; Internal Medicine
Record Identifier: 9984006361202771

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