Expressing acid-sensing ion channel 3 in the brain alters acid-evoked currents and impairs fear conditioning

V C Vralsted; M P Price; J Du; M Schnizler; A M Wunsch; A E Ziemann; M J Welsh; J A Wemmie

doi:10.1111/j.1601-183X.2011.00683.x

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Expressing acid-sensing ion channel 3 in the brain alters acid-evoked currents and impairs fear conditioning

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Expressing acid-sensing ion channel 3 in the brain alters acid-evoked currents and impairs fear conditioning

V C Vralsted, M P Price, J Du, M Schnizler, A M Wunsch, A E Ziemann, M J Welsh and J A Wemmie

Genes, brain and behavior, Vol.10(4), pp.444-450

06/2011

DOI: 10.1111/j.1601-183X.2011.00683.x

PMCID: PMC3107921

PMID: 21324060

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Abstract

Previous studies on mice with a disruption of the gene encoding acid-sensing ion channel 1a (ASIC1a) suggest that ASIC1a is required for normal fear behavior. To investigate the effects of altering the subunit composition of brain ASICs on behavior, we developed transgenic mice expressing ASIC3 via the pan-neuronal synapsin I promoter. These mice express ASIC3 in the brain, where the endogenous ASIC3 protein is not detected. We found that in ASIC3 transgenic mice, ASIC3 co-immunoprecipitated with the endogenous ASIC1a protein and distributed in the same subcellular brain fractions as ASIC1a. In addition, ASIC3 significantly increased the rate of desensitization of acid-evoked currents in cultured cortical neurons. Importantly, ASIC3 reduced Pavlovian fear conditioning to both context and auditory cues. These observations suggest that ASIC3 can heteromultimerize with ASIC1a in the brain and alter the biophysical properties of the endogenous channel complex. Moreover, these data suggest that ASIC subunit composition and channel desensitization may be critical determinants for ASIC-dependent behavior.

Acid-sensing ion channels

amygdala

fear conditioning

Original

ASIC3

Details

Title: Subtitle: Expressing acid-sensing ion channel 3 in the brain alters acid-evoked currents and impairs fear conditioning
Creators: V C Vralsted - Department of Internal Medicine
M P Price - Department of Internal Medicine
J Du - Department of Internal Medicine
M Schnizler - Department of Internal Medicine
A M Wunsch - Department of Psychiatry
A E Ziemann - Department of Molecular Physiology and Biophysics
M J Welsh - Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa
J A Wemmie - Department of Veterans Affairs Medical Center
Resource Type: Journal article
Publication Details: Genes, brain and behavior, Vol.10(4), pp.444-450
DOI: 10.1111/j.1601-183X.2011.00683.x
PMID: 21324060
PMCID: PMC3107921
NLM abbreviation: Genes Brain Behav
ISSN: 1601-1848
eISSN: 1601-183X
Publisher: Blackwell Publishing Ltd; Oxford, UK
Language: English
Date published: 06/2011
Academic Unit: Neurology; Molecular Physiology and Biophysics; Psychiatry; Iowa Neuroscience Institute; Neurosurgery; Internal Medicine
Record Identifier: 9984004180702771

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