Endogenous adenosine can reduce epileptiform activity in the human epileptogenic cortex maintained in vitro.
The effects induced by adenosine and some related compounds upon Mg2+-free epileptogenesis were studied in slices of human epileptogenic neocortex maintained in vitro. Extracellular recordings revealed stimulus-induced and spontaneous epileptiform activity within 1-2 h of perfusion with Mg2+-free medium. A 30-90% decrease of the frequency of occurrence of spontaneous epileptiform discharges was induced by 40-50 microM adenosine while the analog 2-Cl-adenosine exerted a depressant effect (greater than 75% reduction in frequency of occurrence) at 0.3-3 microM. 2-Cl-adenosine also depressed stimulus-induced epileptiform responses and often blocked spontaneous epileptiform activity. Similar effects were seen during bath application of the adenosine uptake inhibitor nitrobenzylthioinosine (10-50 microM) indicating that endogenous adenosine can by itself influence epileptogenicity. Our data demonstrate that in the human epileptogenic neocortex a purinergic mechanism can control Mg2+-free epileptiform activity.
Kostopoulos
G
G
Montreal Neurological Institute, McGill University, Que., Canada.
Drapeau
C
C
Avoli
M
M
Olivier
A
A
Villemeure
J G
JG
D000241:Adenosine / Q000494:pharmacology / Q000502:physiology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D004827:Epilepsy / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D013868:Thioinosine / Q000494:pharmacology / Q000031:analogs & derivatives
D013868:Thioinosine; C001789:4-nitrobenzylthioinosine; D000241:Adenosine