title: Hippocampal slices: glutamate overflow and cellular damage from ischemia are reduced by sodium-channel blockade.
abstract: We evaluated concentrations of excitatory amino acids released from slices into the superfusing solution and also evaluated extracellular field potential recordings and histological appearance of slice tissues to evaluate several sodium-channel modulating drugs as potential treatments for ischemia. The selective sodium-channel blocker tetrodotoxin (TTX, 1 microM) reduced glutamate release from deprivation of oxygen and D-glucose, while calcium-channel blockade was ineffective. Thus, during ischemia, we propose that glutamate may be released from the free cytosolic pool ('metabolic' glutamate) rather than by exocytosis. TTX (100-500 nM) and voltage-dependent sodium-channel blockers (phenytoin, 20-100 microM; lidocaine, 2-200 microM) each prevented damage to slices without blocking action potentials. The reduction of cellular depolarization and sodium loading during ischemia may explain the neuroprotective action of several sodium-channel modulating drugs in our in vitro studies and also in animal models.
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy*; D004594:Electrophysiology; D018698:Glutamic Acid / Q000494:pharmacology*; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D010672:Phenytoin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D026941:Sodium Channel Blockers; D018698:Glutamic Acid; D013779:Tetrodotoxin; D010672:Phenytoin