Glucose-supported oxidative metabolism and evoked potentials are sensitive to fluoroacetate, an inhibitor of glial tricarboxylic acid cycle in the olfactory cortex slice.
Optical absorbance change was measured by reflectance spectrophotometry in the olfactory cortex slice prepared from the rat brain. Optical absorbance of the piriform area of the slice was increased by perifusion with an anoxic (N2-gassed) solution. Components of the absorbance spectrum recorded from the slice in anoxia corresponded to that of cytochromes (cyt) aa3 and c + c1, but did not to that of cyt c. Reduction of cytochromes in anoxia coincided with decrease in the amplitude of the presynaptic potential and a slower negative wave (N-wave). The reduced state of cytochromes switched to an oxidized state when a well-oxygenated solution was reintroduced. An almost complete recovery of redox state coincided with full recovery of the evoked potential. A metabolic inhibitor, 2-deoxy-D-glucose (2DG) (10 mM) or iodoacetic acid (IAA) (3 mM) caused little or slight oxidation of cytochromes, but significantly decreased the amplitude of evoked potentials. Marked oxidation of cytochromes was observed only by perifusion with a solution containing 2 DG (10 mM) and IAA (3 mM). The rate of oxygen uptake was significantly lowered by these metabolic inhibitors. When the slice was perifused with a solution containing fluoroacetate (1 or 10 mM), a selective inhibitor of glial metabolism, cytochromes shifted to oxidized levels. The amplitude of evoked potentials tended to decline by a low dose (1 mM), and significantly decreased by a high dose (10 mM) of fluoroacetate. Oxygen consumption of the slice was dose-relatedly lowered by fluoroacetate.(ABSTRACT TRUNCATED AT 250 WORDS)
Saito
T
T
Department of Physiology, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002952:Citric Acid Cycle / Q000187:drug effects*; D003580:Cytochromes / Q000378:metabolism; D003847:Deoxyglucose / Q000494:pharmacology; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D005463:Fluoroacetates / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D008297:Male; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D003580:Cytochromes; D005463:Fluoroacetates; D007461:Iodoacetates; D003847:Deoxyglucose; C014815:fluoroacetic acid; D005947:Glucose; D019807:Iodoacetic Acid