Nitric Oxide Modulates Low-Mg2+-Induced Epileptiform Activity in Rat Hippocampal–Entorhinal Cortex Slices

Sebastian Schuchmann, Doris Albrecht, Uwe Heinemann, Oliver von Bohlen und Halbach
2002 Neurobiology of Disease  
The production of nitric oxide (NO) during low-Mg 2؉ -induced epileptiform activity in rat hippocampalentorhinal 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 Mg 2؉ ions
more » ... 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-Mg 2؉ 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 M) caused a complete blockade of low-Mg 2؉ -induced epileptiform activity. Under this condition, increasing NO concentration by addition of the NO donor S-nitroso-N-acetylpenicillamine (200 M) reinduced the epileptiform activity. It has been concluded that onset and maintenance of low-Mg 2؉ -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.
doi:10.1006/nbdi.2002.0533 pmid:12460549 fatcat:4herk7szmrf73ozacbb27xvi4q