Nitric oxide modulates low-Mg2+-induced epileptiform activity in rat hippocampal-entorhinal cortex slices

Neurobiol Dis. 2002 Oct;11(1):96-105. doi: 10.1006/nbdi.2002.0533.


The production of nitric oxide (NO) during low-Mg2+-induced epileptiform activity in rat hippocampal-entorhinal cortex slices was investigated by real-time monitoring using 1,2-diaminoanthraquinone (DAQ). NO reacts with the aromatic amino groups of DAQ at neutral pH and in the presence of oxygen to form the fluorescence product 1H-anthra-[1,2d]-[1,2,3]triazole-6,11-dione (ATD). The DAQ-induced formation of ATD required NO and was insensitive to radical oxygen species. Removal of Mg2+ ions from the artificial cerebrospinal fluid (ACSF) induced a significant elevation in the ATD fluorescence signal. The application of L-arginine (2 mM), a substrate of nitric oxide synthase (NOS), caused a comparable increase in the ATD fluorescence signal. Furthermore, ATD signal increase induced either by low-Mg2+ ACSF or by L-arginine was sensitive to N-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor. The application of L-NAME (200 microM) caused a complete blockade of low-Mg2+-induced epileptiform activity. Under this condition, increasing NO concentration by addition of the NO donor S-nitroso-N-acetylpenicillamine (200 microM) reinduced the epileptiform activity. It has been concluded that onset and maintenance of low-Mg2+-induced spontaneous epileptiform activity are modulated by NO concentration. Further NO imaging studies may help to elucidate the role of NO in detail and may bring to light new means for epilepsy therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoquinones
  • Biomarkers
  • Entorhinal Cortex / metabolism*
  • Entorhinal Cortex / physiopathology
  • Enzyme Inhibitors / pharmacology
  • Epilepsy / metabolism*
  • Epilepsy / physiopathology
  • Hippocampus / metabolism*
  • Hippocampus / physiopathology
  • Magnesium / pharmacology*
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / biosynthesis
  • Nitric Oxide / metabolism*
  • Nitric Oxide Donors / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Organ Culture Techniques
  • Penicillamine / analogs & derivatives*
  • Penicillamine / pharmacology
  • Rats
  • Rats, Wistar


  • Benzoquinones
  • Biomarkers
  • Enzyme Inhibitors
  • Nitric Oxide Donors
  • S-nitro-N-acetylpenicillamine
  • Nitric Oxide
  • DAQ
  • Nitric Oxide Synthase
  • Penicillamine
  • Magnesium
  • NG-Nitroarginine Methyl Ester