Potassium channel activators abolish excitotoxicity in cultured hippocampal pyramidal neurons

April E. Abele, Richard J. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

When hippocampal pyramidal neurons are grown in culture they develop excitatory synaptic contacts. If these cultures are perfused with Mg2+-free, glycine supplemented medium the neurons exhibit fluctuations in [Ca2+]i and associated cell death ('excitotoxicity'). These phenomena involve the activation of NMDA receptors. When cultures are treated with the K+-channel activators cromakalim and diazoxide both the [Ca2+]i fluctuations and the neuronal death are abolished. These effects are reversed by the sulfonylurea glyburide. It thus appears that K+-channel activators may be a novel therapeutic intervention in epilepsy and associated disorders.

Original languageEnglish (US)
Pages (from-to)195-200
Number of pages6
JournalNeuroscience Letters
Volume115
Issue number2-3
DOIs
StatePublished - Jul 31 1990

Funding

Supported by PHS Grants DA-02121, 02575 and MH-40165. A.E.A. was supported by Cardiology Training grant HL 07381. The authors are grateful to Wendy and Kenneth Scholz for help with electrophysiology and cell culture techniques to Dr. M. Rogawski for the gift of cromakalim and to Dr. L. Philipson for the gifts of glyburide and diazoxide. In addition we would like to thank Dr. E. Page for the use of the fluorescent microscope.

Keywords

  • Calcium
  • Excitotoxicity
  • Glutamate
  • Hippocampus
  • Potassium channel
  • Sulfonylurea

ASJC Scopus subject areas

  • General Neuroscience

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