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Anticonvulsant effects of the BK-channel antagonist paxilline

Jesse J Sheehan1, Brett L Benedetti, Alison L Barth

  • 1Department of Biological Sciences and Center for the Neural Basis of Cognition, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA.

Epilepsia
|December 5, 2008
PubMed
Abstract

Insights

The BK-channel antagonist paxilline demonstrates significant anticonvulsant effects, effectively eliminating or reducing seizures in rodent models. This finding supports the role of BK channels in seizure activity and suggests a potential therapeutic target for epilepsy.

Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • Mutations in the Ca(2+)- and voltage-gated K(+) channel BK (KCNMA1) are linked to seizure disorders.
  • Seizures induce a gain-of-function in BK channels, increasing neocortical neuron excitability.

Purpose of the Study:

  • To investigate the anticonvulsant potential of BK-channel antagonists in vivo.
  • To determine if blocking BK channel activity can prevent or reduce seizure severity.

Main Methods:

  • Seizures were induced in rodents using GABA(A) antagonists (picrotoxin or pentylenetetrazole).
  • Animals received the BK-channel antagonist paxilline or saline 24 hours after initial seizure induction.
  • The presence, duration, and intensity of tonic-clonic seizures were assessed.

Main Results:

  • Paxilline administration completely prevented tonic-clonic seizures in picrotoxin-treated animals.
  • Paxilline significantly reduced the duration and intensity of seizures in pentylenetetrazole-treated animals.

Conclusions:

  • The BK-channel antagonist paxilline exhibits notable anticonvulsant activity in established rodent seizure models.
  • These findings suggest that targeting BK channels may be a viable strategy for epilepsy treatment, potentially by reversing seizure-induced channel dysfunction.

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