Potassium channel activators abolish excitotoxicity in cultured hippocampal pyramidal neurons.
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.
Abele
A E
AE
Department of Pharmacological Sciences, University of Chicago, IL 60637.
Miller
R J
RJ
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019806:Cromakalim; D003981:Diazoxide / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D003981:Diazoxide