Gap Junctions Involvement in Brain Hyperexcitability Phenomena

Hyperexcitability pathologies, epitomized by epilepsy, are a largely unmet medical need, asking for conceptual developments on the functioning of networks of inter-communicating neurons and glia. Intercellular communication via gap junction (GJ) channels is largely present in mammalian brain. The GJ channels are made of proteins, essentially the connexins (Cxs) widely expressed in brain and in peripheral organs, the most abundant being Cx43. Expression level of Cx43 appears elevated in epileptic brains. Many different compounds actually modify the strength of GJ intercellular communication, though none is specific for GJs. Reference GJ blockers have anticonvulsant effects in numerous experimental models of epilepsy and some data suggest that GJ blockade might specifically act on epileptic hyper-synchrony, a feature hardly targeted by current antiepileptic drugs. The involvement of GJs in migraine is also suggested by recent results.