K+ channel openers protect hippocampal neurons against oxidative injury and amyloid beta-peptide toxicity.
Potassium channel openers (KCOs) such as diazoxide and levochromakalim can protect cardiac myocytes against ischemic injury and neurons against excitotoxic injury, presumably because of their ability to hyperpolarize the plasma membrane and reduce calcium influx. We now report that diazoxide, levocromakalim (LCC), and to a lesser extent pinacidil, protect cultured rat hippocampal neurons against oxidative injury induced by exposure to FeSO4 and amyloid beta-peptide (A beta). Imaging studies of intracellular peroxide levels revealed that KCOs suppressed the generation of peroxides induced by FeSO4 and A beta. KCOs were effective in protecting neurons against oxidative insults in the presence of the K+ channel blockers glibenclimide and 4-aminopyridine indicating that their protective mechanism involved actions in addition to activation of K+ channels. The data suggest that KCOs may be of therapeutic value in an array of neurodegenerative disorders that involve oxidative injury.
Goodman
Y
Y
Department of Anatomy & Neurobiology, University of Kentucky, Lexington 40536-0230, USA.
Mattson
M P
MP
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002478:Cells, Cultured; D003981:Diazoxide / Q000494:pharmacology; D005290:Ferric Compounds / Q000633:toxicity; D006146:Guanidines / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009930:Organic Chemicals; D010084:Oxidation-Reduction; D020110:Pinacidil; D051381:Rats
D016229:Amyloid beta-Peptides; D002120:Calcium Channel Agonists; D005290:Ferric Compounds; D006146:Guanidines; D018696:Neuroprotective Agents; D009930:Organic Chemicals; C102234:levochromakalim; C024823:ferric sulfate; D020110:Pinacidil; D006861:Hydrogen Peroxide; D003981:Diazoxide