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

• Published in: European journal of pharmacology Vol. 403; no. 3; pp. 229 - 233
• Main Authors: Haberek, Grzegorz, Tomczyk, Tomasz, Zuchora, Beata, Wielosz, Marian, Turski, Waldemar A, Urbanska, Ewa M
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 08.09.2000; Elsevier
• Subjects: 3-Nitropropionic acid; 4-Aminopyridine; Acetylcholine - pharmacology; Animals; Biological and medical sciences; Convulsants - pharmacology; Drug Interactions; Drug toxicity and drugs side effects treatment; Electric Stimulation; Electroconvulsion; Electron Transport - drug effects; Electroshock; Excitatory Amino Acid Antagonists - metabolism; GABA (γ-aminobutyric acid); gamma-Aminobutyric Acid - pharmacology; Glycine - pharmacology; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Kynurenic Acid - metabolism; Male; Medical sciences; Mice; Mitochondrial toxin; Nervous system (semeiology, syndromes); Neurology; Nitro Compounds; Pharmacology. Drug treatments; Potassium Channels - drug effects; Potassium Channels - metabolism; Propionates - pharmacology; Seizure; Seizures - chemically induced; Synaptic Transmission - drug effects; Toxicity: nervous system and muscle; GABA (γ-aminobutyric acid); Electroconvulsion; Seizure; 4-Aminopyridine; Mitochondrial toxin; 3-Nitropropionic acid; Pathogenesis; Rodentia; Electrophysiology; Propionic acid derivatives; Depolarization; Vertebrata; Respiratory chain; Mitochondria; Mammalia; Convulsion; Mouse; Animal; Inhibitor; Intracellular; Neurological disorder
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(00)00510-0

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.