Control of Electrical Activity in Central Neurons by Modulating the Gating of Small Conductance Ca2+-activated K+ Channels

Paola Pedarzani, Johannes Mosbacher, Andre Rivard, Lorenzo A. Cingolani, Dominik Oliver, Martin Stocker, John Adelman, Bernd Fakler

Research output: Contribution to journalArticle

179 Citations (Scopus)

Abstract

In most central neurons, action potentials are followed by an afterhyperpolarization (AHP) that controls firing pattern and excitability. The medium and slow components of the AHP have been ascribed to the activation of small conductance Ca2+-activated potassium (SK) channels. Cloned SK channels are heteromeric complexes of SK α-subunits and calmodulin. The channels are activated by Ca2+ binding to calmodulin that induces conformational changes resulting in channel opening, and channel deactivation is the reverse process brought about by dissociation of Ca2+ from calmodulin. Here we show that SK channel gating is effectively modulated by 1-ethyl-2-benzimidazolinone (EBIO). Application of EBIO to cloned SK channels shifts the Ca2+ concentration-response relation into the lower nanomolar range and slows channel deactivation by almost 10-fold. In hippocampal CA1 neurons, EBIO increased both the medium and slow AHP, strongly reducing electrical activity. Moreover, EBIO suppressed the hyperexcitability induced by low Mg2+ in cultured cortical neurons. These results underscore the importance of SK channels for shaping the electrical response patterns of central neurons and suggest that modulating SK channel gating is a potent mechanism for controlling excitability in the central nervous system.

Original languageEnglish (US)
Pages (from-to)9762-9769
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number13
DOIs
StatePublished - Mar 30 2001

Fingerprint

Calcium-Activated Potassium Channels
Neurons
Calmodulin
Small-Conductance Calcium-Activated Potassium Channels
Neurology
Action Potentials
Central Nervous System
Chemical activation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Pedarzani, P., Mosbacher, J., Rivard, A., Cingolani, L. A., Oliver, D., Stocker, M., ... Fakler, B. (2001). Control of Electrical Activity in Central Neurons by Modulating the Gating of Small Conductance Ca2+-activated K+ Channels. Journal of Biological Chemistry, 276(13), 9762-9769. https://doi.org/10.1074/jbc.M010001200

Control of Electrical Activity in Central Neurons by Modulating the Gating of Small Conductance Ca2+-activated K+ Channels. / Pedarzani, Paola; Mosbacher, Johannes; Rivard, Andre; Cingolani, Lorenzo A.; Oliver, Dominik; Stocker, Martin; Adelman, John; Fakler, Bernd.

In: Journal of Biological Chemistry, Vol. 276, No. 13, 30.03.2001, p. 9762-9769.

Research output: Contribution to journalArticle

Pedarzani, P, Mosbacher, J, Rivard, A, Cingolani, LA, Oliver, D, Stocker, M, Adelman, J & Fakler, B 2001, 'Control of Electrical Activity in Central Neurons by Modulating the Gating of Small Conductance Ca2+-activated K+ Channels', Journal of Biological Chemistry, vol. 276, no. 13, pp. 9762-9769. https://doi.org/10.1074/jbc.M010001200
Pedarzani, Paola ; Mosbacher, Johannes ; Rivard, Andre ; Cingolani, Lorenzo A. ; Oliver, Dominik ; Stocker, Martin ; Adelman, John ; Fakler, Bernd. / Control of Electrical Activity in Central Neurons by Modulating the Gating of Small Conductance Ca2+-activated K+ Channels. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 13. pp. 9762-9769.
@article{902e8d81a34f40edafad9177f75eb98f,
title = "Control of Electrical Activity in Central Neurons by Modulating the Gating of Small Conductance Ca2+-activated K+ Channels",
abstract = "In most central neurons, action potentials are followed by an afterhyperpolarization (AHP) that controls firing pattern and excitability. The medium and slow components of the AHP have been ascribed to the activation of small conductance Ca2+-activated potassium (SK) channels. Cloned SK channels are heteromeric complexes of SK α-subunits and calmodulin. The channels are activated by Ca2+ binding to calmodulin that induces conformational changes resulting in channel opening, and channel deactivation is the reverse process brought about by dissociation of Ca2+ from calmodulin. Here we show that SK channel gating is effectively modulated by 1-ethyl-2-benzimidazolinone (EBIO). Application of EBIO to cloned SK channels shifts the Ca2+ concentration-response relation into the lower nanomolar range and slows channel deactivation by almost 10-fold. In hippocampal CA1 neurons, EBIO increased both the medium and slow AHP, strongly reducing electrical activity. Moreover, EBIO suppressed the hyperexcitability induced by low Mg2+ in cultured cortical neurons. These results underscore the importance of SK channels for shaping the electrical response patterns of central neurons and suggest that modulating SK channel gating is a potent mechanism for controlling excitability in the central nervous system.",
author = "Paola Pedarzani and Johannes Mosbacher and Andre Rivard and Cingolani, {Lorenzo A.} and Dominik Oliver and Martin Stocker and John Adelman and Bernd Fakler",
year = "2001",
month = "3",
day = "30",
doi = "10.1074/jbc.M010001200",
language = "English (US)",
volume = "276",
pages = "9762--9769",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "13",

}

TY - JOUR

T1 - Control of Electrical Activity in Central Neurons by Modulating the Gating of Small Conductance Ca2+-activated K+ Channels

AU - Pedarzani, Paola

AU - Mosbacher, Johannes

AU - Rivard, Andre

AU - Cingolani, Lorenzo A.

AU - Oliver, Dominik

AU - Stocker, Martin

AU - Adelman, John

AU - Fakler, Bernd

PY - 2001/3/30

Y1 - 2001/3/30

N2 - In most central neurons, action potentials are followed by an afterhyperpolarization (AHP) that controls firing pattern and excitability. The medium and slow components of the AHP have been ascribed to the activation of small conductance Ca2+-activated potassium (SK) channels. Cloned SK channels are heteromeric complexes of SK α-subunits and calmodulin. The channels are activated by Ca2+ binding to calmodulin that induces conformational changes resulting in channel opening, and channel deactivation is the reverse process brought about by dissociation of Ca2+ from calmodulin. Here we show that SK channel gating is effectively modulated by 1-ethyl-2-benzimidazolinone (EBIO). Application of EBIO to cloned SK channels shifts the Ca2+ concentration-response relation into the lower nanomolar range and slows channel deactivation by almost 10-fold. In hippocampal CA1 neurons, EBIO increased both the medium and slow AHP, strongly reducing electrical activity. Moreover, EBIO suppressed the hyperexcitability induced by low Mg2+ in cultured cortical neurons. These results underscore the importance of SK channels for shaping the electrical response patterns of central neurons and suggest that modulating SK channel gating is a potent mechanism for controlling excitability in the central nervous system.

AB - In most central neurons, action potentials are followed by an afterhyperpolarization (AHP) that controls firing pattern and excitability. The medium and slow components of the AHP have been ascribed to the activation of small conductance Ca2+-activated potassium (SK) channels. Cloned SK channels are heteromeric complexes of SK α-subunits and calmodulin. The channels are activated by Ca2+ binding to calmodulin that induces conformational changes resulting in channel opening, and channel deactivation is the reverse process brought about by dissociation of Ca2+ from calmodulin. Here we show that SK channel gating is effectively modulated by 1-ethyl-2-benzimidazolinone (EBIO). Application of EBIO to cloned SK channels shifts the Ca2+ concentration-response relation into the lower nanomolar range and slows channel deactivation by almost 10-fold. In hippocampal CA1 neurons, EBIO increased both the medium and slow AHP, strongly reducing electrical activity. Moreover, EBIO suppressed the hyperexcitability induced by low Mg2+ in cultured cortical neurons. These results underscore the importance of SK channels for shaping the electrical response patterns of central neurons and suggest that modulating SK channel gating is a potent mechanism for controlling excitability in the central nervous system.

UR - http://www.scopus.com/inward/record.url?scp=0035971096&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035971096&partnerID=8YFLogxK

U2 - 10.1074/jbc.M010001200

DO - 10.1074/jbc.M010001200

M3 - Article

C2 - 11134030

AN - SCOPUS:0035971096

VL - 276

SP - 9762

EP - 9769

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 13

ER -