The role of gap junctions in seizures.
Electrotonic synaptic communication between neurons via gap junctions (gjs) is increasingly recognized as an important synchronizing mechanism in the brain. At the same time, the biology of central nervous system (CNS) gjs is being unravelled. The pathogenesis of the abnormal neuronal synchrony underlying seizures, formerly thought to be based mainly on chemical synaptic transmission, now includes a role for gap junctional communication. This concept has been strengthened by evidence from several in vitro seizure models, in which pharmacological manipulations of gap junctional communication predictably affect the generation of seizures: blockers diminishing seizures and enhancers increasing the seizures. Evidence for interneurons, coupled in part by gjs, generating synchronous neural network activity including seizures, is presented. Also neuromodelling studies, which have enhanced our ability to understand the functional role that gap junctional communication plays in the generation and maintenance of neural synchrony and seizures, are presented. Gap junctional communication appears to be a promising target for the development of future anticonvulsant therapy.
Carlen
P L
PL
Playfair Neuroscience Unit, Toronto Hospital Research Institute and Bloorview Epilepsy Program, University of Toronto, Canada. carlen@playfair.utoronto.ca
Skinner
F
F
Zhang
L
L
Naus
C
C
Kushnir
M
M
Perez Velazquez
J L
JL
D000818:Animals; D004827:Epilepsy / Q000503:physiopathology*; D017629:Gap Junctions / Q000502:physiology*; D006801:Humans; D012640:Seizures / Q000503:physiopathology; D013569:Synapses / Q000502:physiology*