Calpain inhibitor I retards seizure offset in the hippocampus of freely moving rats.
The implications of increased calpain-mediated proteolysis during epileptic seizures are still unclear, and in this study we investigate the effect of the continuous perfusion of calpain inhibitor I on picrotoxin-induced seizures in chronic freely moving rats. Continuous intrahippocampal microperfusion of 500 microM calpain inhibitor I had no effect on basal EEG, but doubled (P < 0.05) average seizure duration, and increased more than five-fold (P < 0.01) the total seizure time and three-fold (P < 0.01) the seizure offset time compared to picrotoxin alone, in each individual rat. However, seizure type and onset time were not modified by calpain inhibitor I. These results indicate that a calpain-mediated mechanism may be responsible for seizure offset, probably through AMPA glutamate receptors internalization and further degradation.
Sierra-Paredes
G
G
Department of Biochemistry and Molecular Biology, School of Medicine, University of Santiago de Compostela, Spain. bngersp@usc.es
Cornes
J M
JM
Sierra-Marcuño
G
G
D000818:Animals; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004569:Electroencephalography / Q000187:drug effects; D006023:Glycoproteins / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010477:Perfusion; D010852:Picrotoxin / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D013997:Time Factors; D014743:Videotape Recording
D015853:Cysteine Proteinase Inhibitors; D006023:Glycoproteins; D010852:Picrotoxin; C039304:calpain inhibitors