Acid sensing ion channels regulate neuronal excitability by inhibiting BK potassium channels

Elena Petroff; Vladislav Snitsarev; Huiyu Gong; Francois M Abboud

doi:10.1016/j.bbrc.2012.08.114

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Acid sensing ion channels regulate neuronal excitability by inhibiting BK potassium channels

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Acid sensing ion channels regulate neuronal excitability by inhibiting BK potassium channels

Elena Petroff, Vladislav Snitsarev, Huiyu Gong and Francois M Abboud

Biochemical and biophysical research communications, Vol.426(4), pp.511-515

10/05/2012

DOI: 10.1016/j.bbrc.2012.08.114

PMCID: PMC3488431

PMID: 22960074

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https://www.ncbi.nlm.nih.gov/pmc/articles/3488431View

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Abstract

► ASICs inhibit BK channels in neurons, this inhibition is relieved by acidification. ► Interaction with ASICs confers pH sensitivity on BK channel. ► ASIC–BK interaction regulates neuronal excitability. Acid sensing ion channels (ASICs), Ca2+ and voltage-activated potassium channels (BK) are widely present throughout the central nervous system. Previous studies have shown that when expressed together in heterologous cells, ASICs inhibit BK channels, and this inhibition is relieved by acidic extracellular pH. We hypothesized that ASIC and BK channels might interact in neurons, and that ASICs may regulate BK channel activity. We found that ASICs inhibited BK currents in cultured wild-type cortical neurons, but not in ASIC1a/2/3 triple knockout neurons. The inhibition in the wild-type was partially relieved by a drop in extracellular pH to 6. To test the consequences of ASIC–BK interaction for neuronal excitability, we compared action potential firing in cultured cortical neurons from wild-type and ASIC1a/2/3 null mice. We found that in the knockout, action potentials were narrow and exhibited increased after-hyperpolarization. Moreover, the excitability of these neurons was significantly increased. These findings are consistent with increased BK channel activity in the neurons from ASIC1a/2/3 null mice. Our data suggest that ASICs can act as endogenous pH-dependent inhibitors of BK channels, and thereby can reduce neuronal excitability.

BK channel

Excitability

Action potential

Acid sensing ion channel

Details

Title: Subtitle: Acid sensing ion channels regulate neuronal excitability by inhibiting BK potassium channels
Creators: Elena Petroff - Department of Biology and Molecular Biology, Montclair State University, Montclair, NJ 07043, USA
Vladislav Snitsarev - Department of Biology and Molecular Biology, Montclair State University, Montclair, NJ 07043, USA
Huiyu Gong - Department of Neonatology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Francois M Abboud - Department of Internal Medicine and Cardiovascular Research Center, Department of Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Biochemical and biophysical research communications, Vol.426(4), pp.511-515
DOI: 10.1016/j.bbrc.2012.08.114
PMID: 22960074
PMCID: PMC3488431
NLM abbreviation: Biochem Biophys Res Commun
ISSN: 0006-291X
eISSN: 1090-2104
Publisher: Elsevier Inc
Language: English
Date published: 10/05/2012
Academic Unit: Molecular Physiology and Biophysics; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
Record Identifier: 9984025420902771

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