Poster: Connexin43 hemichannel inhibition exerts anticonvulsant effects against experimentally induced limbic seizures

Nowadays, the contribution of astrocytic connexin43 hemichannels (Cx43-HCs) to brain functioning and dysfunctioning hasn’t been fully elucidated. In this study, we want to screen Cx43-HCs as novel antiepileptic drug targets through the in vivo screening of a newly developed and selective Cx43-HC-inhibitor (TAT-Gap19) in different acute models of seizures. In the acute pilocarpine rat model, we found that an intrahippocampal perfusion of 12.5 µM TAT-Gap19 was able to significantly reduce the seizure-related behavioural movements (based on Racine’s scale) induced by pilocarpine. In the acute pilocarpine mouse model, ECoG recordings were used to compare seizure severity because of the unclear behaviour in these animals. We found that an intrahippocampal perfusion of 25 µM TAT-Gap19 significantly reduced the total seizure duration (sum of duration of all individual seizures displayed on ECoG recordings). We will also determine the concentration of glutamate and D-serine in the dialysate samples which were collected during this experiment in view of the hypothesis that Cx43-HCs might release these gliotransmitters in vivo. In the six Hertz (6 Hz) mouse model, an electrical model of therapy-resistant seizures, we found that an intracerebroventricular injection of 1 nmol TAT-Gap19 and an intraperitoneal injection of 25 mg/kg TAT-Gap19 leads to a significant decrease in the total seizure duration. These results suggest that Cx43-HCs play a role in seizure generation. Additionally, it is of very high importance to screen TAT-Gap19 in chronic models of epilepsy in order to unravel the role these channels play in epilepsy and epileptogenesis.