Electrophysiological consequences of exposure of hippocampal slices to dihydroxyfumarate, a generator of superoxide radicals.
In an effort to understand the damaging actions of free radicals to neuronal electrophysiology, the superoxide generator, dihydroxyfumarate (DHF), was evaluated in slices of guinea pig hippocampus. Using field potential recording techniques, population spikes and population synaptic potentials were recorded in field CA1. Slices were exposed to 3 mM DHF either alone or in the presence of a protectant. DHF did not alter the ability of the afferent volley to generate a synaptic potential, but it did impair the ability of the synaptic potential to elicit a population spike. In addition, DHF induced lipid peroxidation as measured by the thiobarbituric acid assay. Superoxide dismutase (SOD) provided no protection. Instead, SOD treatment promoted DHF damage to synaptic potentials. Catalase alone mitigated the actions of DHF, but only in SOD plus catalase was the DHF-induced electrophysiological deficit and lipid peroxidation completely antagonized. The iron chelator, Desferal, did not protect but promoted synaptic damage. Desferal may be ineffective because of the nitroxide radical formed upon its reaction with DHF. The hydroxyl radical scavenger, dimethylsulfoxide, prevented lipid peroxidation and reduced the DHF-induced deficit but did not completely prevent the impairment of spike generation. These data suggest that DHF exerts its actions through generation of hydrogen peroxide which would further react with tissue iron to produce hydroxyl radicals.
Pellmar
T C
TC
Physiology Department, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889.
Lepinski
D L
DL
D000818:Animals; D002374:Catalase / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects; D005650:Fumarates / Q000494:pharmacology*; D006168:Guinea Pigs; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology
D005650:Fumarates; D013481:Superoxides; C005998:dihydroxyfumarate; D008315:Malondialdehyde; D002374:Catalase; D013482:Superoxide Dismutase; D003676:Deferoxamine; D004121:Dimethyl Sulfoxide