ASIC2 Subunits Target Acid-Sensing Ion Channels to the Synapse via an Association with PSD-95

Xiang-ming Zha; Vivian Costa; Anne Marie S Harding; Leah Reznikov; Christopher J Benson; Michael J Welsh

doi:10.1523/JNEUROSCI.1284-09.2009

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ASIC2 Subunits Target Acid-Sensing Ion Channels to the Synapse via an Association with PSD-95

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ASIC2 Subunits Target Acid-Sensing Ion Channels to the Synapse via an Association with PSD-95

Xiang-ming Zha, Vivian Costa, Anne Marie S Harding, Leah Reznikov, Christopher J Benson and Michael J Welsh

The Journal of neuroscience, Vol.29(26), pp.8438-8446

07/01/2009

DOI: 10.1523/JNEUROSCI.1284-09.2009

PMCID: PMC2734339

PMID: 19571134

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Abstract

Acid-sensing ion channel-1a (ASIC1a) mediates H + -gated current to influence normal brain physiology and impact several models of disease. Although ASIC2 subunits are widely expressed in brain and modulate ASIC1a current, their function remains poorly understood. We identified ASIC2a in dendrites, dendritic spines, and brain synaptosomes. This localization largely relied on ASIC2a binding to PSD-95 and matched that of ASIC1a, which does not coimmunoprecipitate with PSD-95. We found that ASIC2 and ASIC1a associated in brain, and through its interaction with PSD-95, ASIC2 increased ASIC1a localization in dendritic spines. Consistent with earlier work showing that acidic pH elevated spine [Ca 2+ ] i by activating ASIC1a, loss of ASIC2 decreased the percentage of spines responding to acid. Moreover, like a reduction of ASIC1a, the number of spine synapses fell in ASIC2 −/− neurons. These results indicate that ASIC2 facilitates ASIC1a localization and function in dendritic spines and suggest that the two subunits work in concert to regulate neuronal function.

Details

Title: Subtitle: ASIC2 Subunits Target Acid-Sensing Ion Channels to the Synapse via an Association with PSD-95
Creators: Xiang-ming Zha - Howard Hughes Medical Institute
Vivian Costa - Neuroscience Program, and
Anne Marie S Harding - Departments of Internal Medicine and
Leah Reznikov - Howard Hughes Medical Institute
Christopher J Benson - Neuroscience Program, and
Michael J Welsh - Howard Hughes Medical Institute
Resource Type: Journal article
Publication Details: The Journal of neuroscience, Vol.29(26), pp.8438-8446
Publisher: Society for Neuroscience
DOI: 10.1523/JNEUROSCI.1284-09.2009
PMID: 19571134
PMCID: PMC2734339
ISSN: 0270-6474
eISSN: 1529-2401
Language: English
Date published: 07/01/2009
Academic Unit: Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Neurosurgery; Internal Medicine
Record Identifier: 9984020642002771

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