Potentiation of cyanide neurotoxicity by blockade of ATP-sensitive potassium channels.

Exposure of primary hippocampal cultures to NaCN (2 mM) or glyburide (5 microM) alone for 3 h did not produce a rise in extracellular lactic dehydrogenase (LDH) activity. Coincubation with NaCN and glyburide produced a significant efflux of LDH from the neurons. Diazoxide or D-2-amino-5-phosphovalerate (APV) partially reversed the release of LDH by the combination of NaCN and glyburide. These observations indicate ATP-sensitive potassium channels (KATP) are activated by nonlethal concentrations of cyanide and their blockade with glyburide unmasks cyanide's toxicity. The cytotoxicity of cyanide appears to result from a combination of processes resulting in altered ion handling and excitotoxicity.