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.
Patel
M N
MN
Department of Pharmacology and Toxicology, Purdue University, West Lafayette, IN 47907.
Yim
G K
GK
Isom
G E
GE
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D003981:Diazoxide / Q000633:toxicity*; D004357:Drug Synergism; D005905:Glyburide / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D009498:Neurotoxins / Q000633:toxicity*; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D012966:Sodium Cyanide / Q000633:toxicity*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
D009498:Neurotoxins; D015221:Potassium Channels; C056639:2-amino-5-phosphopentanoic acid; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D014633:Valine; D003981:Diazoxide; D012966:Sodium Cyanide; D005905:Glyburide