Poster: Involvement of astrocytic connexin43-based hemichannels in mechanisms of limbic seizures

Epilepsy is a complex neurological disorder that affects approximately 50 million people worldwide. Despite the fact that numerous new antiepileptic drugs (AEDs) became available in the last decade, approximately 30% of all epilepsy patients remain resistant to any pharmacological intervention. Furthermore, the marketed drugs are not completely without side effects. Therefore, the search for new therapies with a safer therapeutic index and better efficacy is clearly warranted. The goal of the current study is to screen connexin43 (Cx43)-based hemichannels (HCs) as novel antiepileptic drug targets through the application of TAT-Gap19, a newly developed and selective Cx43 HC-inhibitor.

Accumulating evidence points to a prominent role for Cx43 signaling in epilepsy. Compelling in vivo evidence for the contribution of Cx43 HCs to brain functioning is still lacking, mainly because of the paucity of appropriate tools allowing selective targeting of Cx43 HCs, as all known pharmacological blockers available to date inhibit both gap junctions (GJs) and HCs. Furthermore, Cx43 knockout (KO) mice are not suitable neither to discriminate GJ and HC functions as both channels are Cx43-based. An exception is made for TAT-Gap19, a Cx mimetic peptide which inhibits Cx43 HCs but not GJs in in vivo settings. This peptide is now at our disposal to study for the first time the in vivo role of the Cx43 HCs in mechanisms of limbic seizures, by using the intracereberal microdialysis technique.