Extracellular Chloride Modulates the Desensitization Kinetics of Acid-sensing Ion Channel 1a (ASIC1a)

Nobuyoshi Kusama; Anne Marie S Harding; Christopher J Benson

doi:10.1074/jbc.M109.091561

Back

Extracellular Chloride Modulates the Desensitization Kinetics of Acid-sensing Ion Channel 1a (ASIC1a)

Journal article

Open access

Peer reviewed

Extracellular Chloride Modulates the Desensitization Kinetics of Acid-sensing Ion Channel 1a (ASIC1a)

Nobuyoshi Kusama, Anne Marie S Harding and Christopher J Benson

The Journal of biological chemistry, Vol.285(23), pp.17425-17431

06/04/2010

DOI: 10.1074/jbc.M109.091561

PMCID: PMC2878506

PMID: 20385551

Files and links (1)

url

https://doi.org/10.1074/jbc.M109.091561View

Published (Version of record) Open Access

Abstract

Acid-sensing ion channels (ASICs) are sodium channels gated by extracellular protons. The recent crystallization of ASIC1a identified potential binding sites for Cl − in the extracellular domain that are highly conserved between ASIC isoforms. However, the significance of Cl − binding is unknown. We investigated the effect of Cl − substitution on heterologously expressed ASIC1a current and H + -gated currents from hippocampal neurons recorded by whole-cell patch clamp. Replacement of extracellular Cl − with the impermeable and inert anion methanesulfonate (MeSO 3 − ) caused ASIC1a currents to desensitize at a faster rate and attenuated tachyphylaxis. However, peak current amplitude, pH sensitivity, and selectivity were unchanged. Other anions, including Br − , I − , and thiocyanate, also altered the kinetics of desensitization and tachyphylaxis. Mutation of the residues that form the Cl − -binding site in ASIC1a abolished the modulatory effects of anions. The results of anion substitution on native ASIC channels in hippocampal neurons mirrored those in heterologously expressed ASIC1a and altered acid-induced neuronal death. Anion modulation of ASICs provides new insight into channel gating and may prove important in pathological brain conditions associated with changes in pH and Cl − .

Protons

Neuron

Chloride

Ion Channels

Cell Surface Protein

Membrane Biology

Biophysics

Acid-sensing Ion Channels (ASIC)

Details

Title: Subtitle: Extracellular Chloride Modulates the Desensitization Kinetics of Acid-sensing Ion Channel 1a (ASIC1a)
Creators: Nobuyoshi Kusama - From the Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242
Anne Marie S Harding - From the Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242
Christopher J Benson - From the Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.285(23), pp.17425-17431
DOI: 10.1074/jbc.M109.091561
PMID: 20385551
PMCID: PMC2878506
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: American Society for Biochemistry and Molecular Biology; 9650 Rockville Pike, Bethesda, MD 20814, U.S.A
Grant note: HL076419 / National Institutes of Health
Language: English
Date published: 06/04/2010
Academic Unit: Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040435402771

Metrics

22 Record Views

33 Times Cited - Web of Science