Proconvulsive effects of the mitochondrial respiratory chain inhibitor - 3-nitropropionic acid

The role of impaired mitochondrial function in processes leading to the gen eration of seizures was studied in mice. An inhibitor of mitochondrial comp lex III, 3-nitropropionic acid, which is known to evoke convulsions per se, and was used here in subthreshold dose, enhanced seizures generated by ele ctric current and application of 4-aminopyridine. In contrast, 3-nitropropi onic acid did not affect convulsions induced by gamma-aminobutyric acid (GA BA) receptor antagonists - bicuculline, pentylenetetrazol and picrotoxin, g lycine antagonist - strychnine, cholinomimetic drug-pilocarpine, and kynure nine aminotransferase inhibitor - aminooxyacetic acid. It is hypothesised t hat deranged mitochondrial metabolism renders the central nervous system mo re susceptible to factors inducing seizures via direct depolarization. (C) 2000 Elsevier Science B.V. All rights reserved.