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

Abstract

The role of impaired mitochondrial function in processes leading to the generation of seizures was studied in mice. An inhibitor of mitochondrial complex III, 3-nitropropionic acid, which is known to evoke convulsions per se, and was used here in subthreshold dose, enhanced seizures generated by electric current and application of 4-aminopyridine. In contrast, 3-nitropropionic acid did not affect convulsions induced by γ-aminobutyric acid (GABA) receptor antagonists — bicuculline, pentylenetetrazol and picrotoxin, glycine antagonist — strychnine, cholinomimetic drug–pilocarpine, and kynurenine aminotransferase inhibitor — aminooxyacetic acid. It is hypothesised that deranged mitochondrial metabolism renders the central nervous system more susceptible to factors inducing seizures via direct depolarization.