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.