Acid-sensing ion channel 2 (ASIC2) modulates ASIC1 H+-activated currents in hippocampal neurons

Candice C Askwith; John A Wemmie; Margaret P Price; Tania Rokhlina; Michael J Welsh

doi:10.1074/jbc.m312145200

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Acid-sensing ion channel 2 (ASIC2) modulates ASIC1 H+-activated currents in hippocampal neurons

Journal article

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Peer reviewed

Acid-sensing ion channel 2 (ASIC2) modulates ASIC1 H+-activated currents in hippocampal neurons

Candice C Askwith, John A Wemmie, Margaret P Price, Tania Rokhlina and Michael J Welsh

The Journal of biological chemistry, Vol.279(18), pp.18296-18305

04/30/2004

DOI: 10.1074/jbc.m312145200

PMID: 14960591

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Abstract

Hippocampal neurons express subunits of the acid-sensing ion channel (ASIC1 and ASIC2) and exhibit large cation currents that are transiently activated by acidic extracellular solutions. Earlier work indicated that ASIC1 contributed to the current in these neurons and suggested its importance for normal behavior. However, the specific contribution of ASIC1 and ASIC2 subunits to acid-evoked currents in hippocampal neurons remained uncertain. To decipher the individual role of the ASIC subunits, we studied H(+)-gated currents in neurons from both ASIC1 and ASIC2 null mice. We found that much of the current was produced by ASIC1a/2a heteromultimeric channels, and individual subunits made distinct contributions. The ASIC1a subunit was key in establishing current amplitude. The ASIC2a subunit had little effect on amplitude but influenced desensitization, recovery from desensitization, pH sensitivity, and the response to modulatory agents. We also found heterogeneity in the contribution of ASIC2 throughout the neuronal population, with individual neurons expressing both ASIC1a homomultimeric and ASIC1a/2a heteromultimeric channels. Studies of neurons heterozygous for disrupted ASIC alleles indicated that the properties of H(+)-gated currents are dependent on the proportion of the individual subunits. These findings indicate that the absolute and relative amounts of ASIC subunits determine the amplitude and properties of hippocampal H(+)-gated currents and therefore may contribute to normal physiology and pathophysiology.

Protons

Nerve Tissue Proteins - physiology

Neurons - chemistry

Acid Sensing Ion Channels

Cells, Cultured

Electrophysiology

Sodium Channels - physiology

Hippocampus - cytology

Mice, Knockout

Nerve Tissue Proteins - chemistry

Animals

Membrane Proteins - chemistry

Sodium Channels - chemistry

Membrane Proteins - physiology

Neurons - physiology

Benzamides - pharmacology

Mice

Neurons - metabolism

Protein Subunits - chemistry

Protein Subunits - physiology

Zinc - pharmacology

FMRFamide - pharmacology

Hydrogen-Ion Concentration

Details

Title: Subtitle: Acid-sensing ion channel 2 (ASIC2) modulates ASIC1 H+-activated currents in hippocampal neurons
Creators: Candice C Askwith - Department of Internal Medicine, Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA
John A Wemmie
Margaret P Price
Tania Rokhlina
Michael J Welsh
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.279(18), pp.18296-18305
DOI: 10.1074/jbc.m312145200
PMID: 14960591
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: HL61234 / NHLBI NIH HHS DK54759 / NIDDK NIH HHS
Language: English
Date published: 04/30/2004
Academic Unit: Neurology; Molecular Physiology and Biophysics; Psychiatry; Iowa Neuroscience Institute; Neurosurgery; Internal Medicine
Record Identifier: 9984003462402771

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