Effects of gap junction blockers on human neocortical synchronization.
Field potentials and intracellular recordings were obtained from human neocortical slices to study the role of gap junctions (GJ) in neuronal network synchronization. First, we examined the effects of GJ blockers (i.e., carbenoxolone, octanol, quinine, and quinidine) on the spontaneous synchronous events (duration = 0.2-1.1 s; intervals of occurrence = 3-27 s) generated by neocortical slices obtained from temporal lobe epileptic patients during application of 4-aminopyridine (4AP, 50 muM) and glutamatergic receptor antagonists. The synchronicity of these potentials (recorded at distances up to 5 mm) was decreased by GJ blockers within 20 min of application, while prolonged GJ blockers treatment at higher doses made them disappear with different time courses. Second, we found that slices from patients with focal cortical dysplasia (FCD) could generate in normal medium spontaneous synchronous discharges (duration = 0.4-8 s; intervals of occurrence = 0.5-90 s) that were (i) abolished by NMDA receptor antagonists and (ii) slowed down by carbenoxolone. Finally, octanol or carbenoxolone blocked 4AP-induced ictal-like discharges (duration = up to 35 s) in FCD slices. These data indicate that GJ play a role in synchronizing human neocortical networks and may implement epileptiform activity in FCD.
Gigout
S
S
INSERM U 573, Paris, 75014 France.
Louvel
J
J
Kawasaki
H
H
D'Antuono
M
M
Armand
V
V
Kurcewicz
I
I
Olivier
A
A
Laschet
J
J
Turak
B
B
Devaux
B
B
Pumain
R
R
Avoli
M
M
D015761:4-Aminopyridine / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000368:Aged; D001927:Brain Diseases / Q000503:physiopathology; D002229:Carbenoxolone / Q000494:pharmacology; D002648:Child; D003344:Cortical Synchronization / Q000187:drug effects; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D017629:Gap Junctions / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008875:Middle Aged; D019579:Neocortex / Q000187:drug effects / Q000502:physiology*; D000442:Octanols / Q000494:pharmacology; D009924:Organ Culture Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011802:Quinidine / Q000494:pharmacology; D011803:Quinine / Q000494:pharmacology; D018079:Receptors, GABA / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism
D018683:Excitatory Amino Acid Agents; D000442:Octanols; D026902:Potassium Channel Blockers; D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate; D011803:Quinine; D015761:4-Aminopyridine; D011802:Quinidine; D002229:Carbenoxolone