Bicuculline block of small-conductance calcium-activated potassium channels

Radwan Khawaled, Andrew Bruening-Wright, John Adelman, James Maylie

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

Small-conductance calcium-activated potassium channels (SK channels) are gated solely by intracellular calcium ions and their activity is responsible for the slow afterhyperpolarization (AHP) that follows an action potential in many excitable cells. Brain slice studies commonly employ a methyl derivative of bicuculline (bicuculline-m), a GABA(A) (γ-aminobutyric acid) receptor antagonist, to diminish the tonic inhibitory influences of GABAergic synapses, or to investigate the role of these synapses in specialized neural networks. However, recent evidence suggests that bicuculline-m may not be specific for GABA(A) receptors and may also block the slow AHP. Therefore, the effects of bicuculline-m on cloned apamin-sensitive SK2 and apamin- insensitive SK1 channels were examined following expression in Xenopus oocytes. The results show that at concentrations employed for slice recordings, bicuculline-m potently blocks both apamin-sensitive SK2 currents and apamin-insensitive SK1 currents when applied to outside-out patches. Apamin-insensitive SK1 currents run down in excised patches. The potency of bicuculline-m block also decreases with time after patch excision. Site- directed mutagenesis that changes two residues in the outer vestibule of the SK1 pore that confers apamin sensitivity also reduces run down of the current in patches, and endows stable sensitivity to bicuculline-m indistinguishable from SK2. Therefore, the use of bicuculline-m in slice recordings may mask apamin-sensitive slow AHPs that are important determinants of neuronal excitability. In addition, bicuculline-m-insensitive slow AHPs may indicate that the underlying channels have run down.

Original languageEnglish (US)
Pages (from-to)314-321
Number of pages8
JournalPflugers Archiv European Journal of Physiology
Volume438
Issue number3
DOIs
StatePublished - 1999

Fingerprint

Small-Conductance Calcium-Activated Potassium Channels
Bicuculline
Apamin
Synapses
Aminobutyrates
Mutagenesis
GABA-A Receptors
Masks
Xenopus
Site-Directed Mutagenesis
gamma-Aminobutyric Acid
Action Potentials
Oocytes
Brain

Keywords

  • Bicuculline block
  • GABA(A) receptors
  • SK channels
  • Slow afterhyperpolarization

ASJC Scopus subject areas

  • Physiology

Cite this

Bicuculline block of small-conductance calcium-activated potassium channels. / Khawaled, Radwan; Bruening-Wright, Andrew; Adelman, John; Maylie, James.

In: Pflugers Archiv European Journal of Physiology, Vol. 438, No. 3, 1999, p. 314-321.

Research output: Contribution to journalArticle

Khawaled, Radwan ; Bruening-Wright, Andrew ; Adelman, John ; Maylie, James. / Bicuculline block of small-conductance calcium-activated potassium channels. In: Pflugers Archiv European Journal of Physiology. 1999 ; Vol. 438, No. 3. pp. 314-321.
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