Acid-sensing ion channels (ASICs) are differentially modulated by anions dependent on their subunit composition

Nobuyoshi Kusama; Mamta Gautam; Anne Marie S Harding; Peter M Snyder; Christopher J Benson

doi:10.1152/ajpcell.00216.2012

Back

Acid-sensing ion channels (ASICs) are differentially modulated by anions dependent on their subunit composition

Journal article

Open access

Peer reviewed

Acid-sensing ion channels (ASICs) are differentially modulated by anions dependent on their subunit composition

Nobuyoshi Kusama, Mamta Gautam, Anne Marie S Harding, Peter M Snyder and Christopher J Benson

American Journal of Physiology: Cell Physiology, Vol.304(1), pp.C89-C101

01/01/2013

DOI: 10.1152/ajpcell.00216.2012

PMCID: PMC3543573

PMID: 23135698

Files and links (1)

url

https://doi.org/10.1152/ajpcell.00216.2012View

Published (Version of record) Open Access

Abstract

Acid-sensing ion channels (ASICs) are sodium channels gated by extracellular protons. ASIC1a channels possess intersubunit Cl − -binding sites in the extracellular domain, which are highly conserved between ASIC subunits. We previously found that anions modulate ASIC1a gating via these sites. Here we investigated the effect of anion substitution on native ASICs in rat sensory neurons and heterologously expressed ASIC2a and ASIC3 channels by whole cell patch clamp. Similar to ASIC1a, anions modulated the kinetics of desensitization of other ASIC channels. However, unlike ASIC1a, anions also modulated the pH dependence of activation. Moreover, the order of efficacy of different anions to modulate ASIC2a and -3 was very different from that of ASIC1a. More surprising, mutations of conserved residues that form an intersubunit Cl − -binding site in ASIC1a only partially abrogated the effects of anion modulation of ASIC2a and had no effect on anion modulation of ASIC3. The effects of anions on native ASICs in rat dorsal root ganglion neurons mimicked those in heterologously expressed ASIC1a/3 heteromeric channels. Our data show that anions modulate a variety of ASIC properties and are dependent on the subunit composition, and the mechanism of modulation for ASIC2a and -3 is distinct from that of ASIC1a. We speculate that modulation of ASIC gating by Cl − is a novel mechanism to sense shifts in extracellular fluid composition.

protons

ASICs

ion channels

Details

Title: Subtitle: Acid-sensing ion channels (ASICs) are differentially modulated by anions dependent on their subunit composition
Creators: Nobuyoshi Kusama - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa; and
Mamta Gautam - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa; and
Anne Marie S Harding - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa; and
Peter M Snyder - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa; and
Christopher J Benson - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa; and
Resource Type: Journal article
Publication Details: American Journal of Physiology: Cell Physiology, Vol.304(1), pp.C89-C101
DOI: 10.1152/ajpcell.00216.2012
PMID: 23135698
PMCID: PMC3543573
NLM abbreviation: Am J Physiol Cell Physiol
ISSN: 0363-6143
eISSN: 1522-1563
Publisher: American Physiological Society; Bethesda, MD
Language: English
Date published: 01/01/2013
Academic Unit: Molecular Physiology and Biophysics; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Medicine Administration; Internal Medicine
Record Identifier: 9984025676902771

Metrics

34 Record Views

16 Times Cited - Web of Science