Acid-sensing ion channels interact with and inhibit BK K+ channels

Elena Yermolaieva Petroff; Margaret P Price; Vladislav Snitsarev; Huiyu Gong; Victoria Korovkina; Francois M Abboud; Michael J Welsh

doi:10.1073/pnas.0712280105

Back

Acid-sensing ion channels interact with and inhibit BK K+ channels

Journal article

Open access

Peer reviewed

Acid-sensing ion channels interact with and inhibit BK K+ channels

Elena Yermolaieva Petroff, Margaret P Price, Vladislav Snitsarev, Huiyu Gong, Victoria Korovkina, Francois M Abboud and Michael J Welsh

Proceedings of the National Academy of Sciences - PNAS, Vol.105(8), pp.3140-3144

02/26/2008

DOI: 10.1073/pnas.0712280105

PMCID: PMC2268598

PMID: 18287010

Files and links (1)

url

https://doi.org/10.1073/pnas.0712280105View

Published (Version of record) Open Access

Abstract

Acid-sensing ion channels (ASICs) are neuronal non-voltage-gated cation channels that are activated when extracellular pH falls. They contribute to sensory function and nociception in the peripheral nervous system, and in the brain they contribute to synaptic plasticity and fear responses. Some of the physiologic consequences of disrupting ASIC genes in mice suggested that ASIC channels might modulate neuronal function by mechanisms in addition to their H + -evoked opening. Within ASIC channel's large extracellular domain, we identified sequence resembling that in scorpion toxins that inhibit K + channels. Therefore, we tested the hypothesis that ASIC channels might inhibit K + channel function by coexpressing ASIC1a and the high-conductance Ca 2+ - and voltage-activated K + (BK) channel. We found that ASIC1a associated with BK channels and inhibited their current. Reducing extracellular pH disrupted the association and relieved the inhibition. BK channels, in turn, altered the kinetics of ASIC1a current. In addition to BK, ASIC1a inhibited voltage-gated Kv1.3 channels. Other ASIC channels also inhibited BK, although acidosis-dependent relief of inhibition varied. These results reveal a mechanism of ion channel interaction and reciprocal regulation. Finding that a reduced pH activated ASIC1a and relieved BK inhibition suggests that extracellular protons may enhance the activity of channels with opposing effects on membrane voltage. The wide and varied expression patterns of ASICs, BK, and related K + channels suggest broad opportunities for this signaling system to alter neuronal function.

Biological Sciences

Details

Title: Subtitle: Acid-sensing ion channels interact with and inhibit BK K+ channels
Creators: Elena Yermolaieva Petroff - Departments of Internal Medicine and
Margaret P Price - Departments of Internal Medicine and
Vladislav Snitsarev - Departments of Internal Medicine and
Huiyu Gong - Departments of Internal Medicine and
Victoria Korovkina - Molecular Physiology and Biophysics and
Francois M Abboud - Departments of Internal Medicine and
Michael J Welsh - Departments of Internal Medicine and
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.105(8), pp.3140-3144
DOI: 10.1073/pnas.0712280105
PMID: 18287010
PMCID: PMC2268598
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 02/26/2008
Academic Unit: Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Internal Medicine
Record Identifier: 9984014019502771

Metrics

30 Record Views

37 Times Cited - Web of Science