Acid-sensing ion channels (ASICs) in mouse skeletal muscle afferents are heteromers composed of ASIC1a, ASIC2, and ASIC3 subunits

Mamta Gautam; Christopher J Benson

doi:10.1096/fj.12-220400

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Acid-sensing ion channels (ASICs) in mouse skeletal muscle afferents are heteromers composed of ASIC1a, ASIC2, and ASIC3 subunits

Journal article

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Peer reviewed

Acid-sensing ion channels (ASICs) in mouse skeletal muscle afferents are heteromers composed of ASIC1a, ASIC2, and ASIC3 subunits

Mamta Gautam and Christopher J Benson

The FASEB journal, Vol.27(2), pp.793-802

02/2013

DOI: 10.1096/fj.12-220400

PMCID: PMC3545527

PMID: 23109675

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https://europepmc.org/articles/pmc3545527View

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Abstract

Acid-sensing ion channels (ASICs) are expressed in skeletal muscle afferents, in which they sense extracellular acidosis and other metabolites released during ischemia and exercise. ASICs are formed as homotrimers or heterotrimers of several isoforms (ASIC1a, ASIC1b, ASIC2a, ASIC2b, and ASIC3), with each channel displaying distinct properties. To dissect the ASIC composition in muscle afferents, we used whole-cell patch-clamp recordings to study the properties of acid-evoked currents (amplitude, pH sensitivity, the kinetics of desensitization and recovery from desensitization, and pharmacological modulation) in isolated, labeled mouse muscle afferents from wild-type (C57BL/6J) and specific ASIC(-/-) mice. We found that ASIC-like currents in wild-type muscle afferents displayed fast desensitization, indicating that they are carried by heteromeric channels. Currents from ASIC1a(-/-) muscle afferents were less pH-sensitive and displayed faster recovery, currents from ASIC2(-/-) mice showed diminished potentiation by zinc, and currents from ASIC3(-/-) mice displayed slower desensitization than those from wild-type mice. Finally, ASIC-like currents were absent from triple-null mice lacking ASIC1a, ASIC2a, and ASIC3. We conclude that ASIC1a, ASIC2a, and ASIC3 heteromers are the principle channels in skeletal muscle afferents. These results will help us understand the role of ASICs in exercise physiology and provide a molecular target for potential drug therapies to treat muscle pain.

Acid Sensing Ion Channels - chemistry

Acid Sensing Ion Channels - deficiency

Acid Sensing Ion Channels - genetics

Acid Sensing Ion Channels - metabolism

Animals

Electrophysiological Phenomena

Ganglia, Spinal - metabolism

Hydrogen-Ion Concentration

Mice

Mice, Inbred C57BL

Mice, Knockout

Muscle, Skeletal - innervation

Muscle, Skeletal - metabolism

Neurons, Afferent - metabolism

Patch-Clamp Techniques

Protein Structure, Quaternary

Protein Subunits

Sensory Receptor Cells - metabolism

Details

Title: Subtitle: Acid-sensing ion channels (ASICs) in mouse skeletal muscle afferents are heteromers composed of ASIC1a, ASIC2, and ASIC3 subunits
Creators: Mamta Gautam - Department of Internal MedicineRoy J. and Lucille A. Carver College of MedicineUniversity of IowaIowa CityIowaUSA
Christopher J Benson - Department of Internal MedicineRoy J. and Lucille A. Carver College of MedicineUniversity of IowaIowa CityIowaUSA
Resource Type: Journal article
Publication Details: The FASEB journal, Vol.27(2), pp.793-802
DOI: 10.1096/fj.12-220400
PMID: 23109675
PMCID: PMC3545527
ISSN: 0892-6638
eISSN: 1530-6860
Grant note: R01 HL107529 / NHLBI NIH HHS
Language: English
Date published: 02/2013
Academic Unit: Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984303746502771

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