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

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

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Abstract

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.

Original languageEnglish
Pages (from-to)511-515
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume426
Issue number4
DOIs
StatePublished - 5 Oct 2012

Fingerprint

Acid Sensing Ion Channels
Large-Conductance Calcium-Activated Potassium Channels
Potassium Channels
Neurons
Action Potentials
Neurology
Central Nervous System
Electric potential

Keywords

  • Acid sensing ion channel
  • Action potential
  • BK channel
  • Excitability

Cite this

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abstract = "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.",
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Acid sensing ion channels regulate neuronal excitability by inhibiting BK potassium channels. / Petroff, Elena; Snitsarev, Vladislav; Gong, Huiyu; Abboud, Francois M.

In: Biochemical and Biophysical Research Communications, Vol. 426, No. 4, 05.10.2012, p. 511-515.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Gong, Huiyu

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