Effects of metabolic inhibitors on evoked activity and the energy state of hippocampal slices superfused in vitro.

The effects of the metabolic inhibitors, arsenate (1,10 mM), iodoacetate (1 mM), alpha-cyano-4-hydroxycinnamate (alpha C4HC: 0.05, 0.15, 0.5 mM), malonate (10 mM) and 2,4-dinitrophenol (10 microM) on granule cell evoked activity and levels of energy metabolites of superfused hippocampal slices were investigated. Every inhibitor tested decreased the amplitudes of the population spikes, and also to a lesser extent, the rates of rise of EPSP. The effects were essentially reversible except in the case of iodoacetate. Concentrations of inhibitors, sufficient to depress evoked activity by at least 75%, did not significantly decrease tissue levels of phosphocreatine, ATP or total K+, with the exception of 1 mM iodoacetate. In slices superfused with 10 mM arsenate, 0.5 mM alpha C4HC, 10 mM malonate or 10 micron 2,4-dinitrophenol, the threshold EPSP for population spike generation was significantly higher than in inhibitor-free medium. These results are discussed in relation to the potential importance of non-oxidative glucose metabolism in maintaining evoked activity, and the possibility that during metabolic insults, tissue ATP utilisation is decreased to match reduced cytoplasmic ATP supply.