HIPPOCAMPAL SLICES - GLUTAMATE OVERFLOW AND CELLULAR-DAMAGE FROM ISCHEMIA ARE REDUCED BY SODIUM-CHANNEL BLOCKADE

We evaluated concentrations of excitatory amino acids released from sl ices into the superfusing solution and also evaluated extracellular fi eld potential recordings and histological appearance of slice tissues to evaluate several sodium channel modulating drugs as potential treat ments for ischemia. The selective sodium-channel blocker tetrodotoxin (TTX, 1 mu M) reduced glutamate release from deprivation of oxygen and D-glucose, while calcium-channel blockade was ineffective. Thus, duri ng ischemia, we propose that glutamate may be released from the free c ytosolic pool ('metabolic' glutamate) rather than by exocytosis. TTX ( 100-500 nM) and voltage-dependent sodium-channel blockers (phenytoin, 20-100 mu M; lidocaine, 2-200 mu M) each prevented damage to slices wi thout blocking action potentials. The reduction of cellular depolariza tion and sodium loading during ischemia may explain the neuroprotectiv e action of several sodium-channel modulating drugs in our in vitro st udies and also in animal models.