Connexin36 gap junction blockade is ineffective at reducing seizure-like event activity in neocortical mouse slices.

Despite much research, there remains controversy over the role of gap junctions in seizure processes. Many studies report anticonvulsant effects of gap junction blockade, but contradictory results have also been reported. The aim of this study was to clarify the role of connexin36 (Cx36) gap junctions in neocortical seizures. We used the mouse neocortical slice preparation to investigate the effect of pharmacological (mefloquine) and genetic (Cx36 knockout mice (Cx36KO)) manipulation of Cx36 gap junctions on two seizure models: low-magnesium artificial cerebrospinal fluid (ACSF) and aconitine perfusion in low-magnesium ACSF. Low-magnesium- (nominally zero) and aconitine- (230 nM) induced seizure-like event (SLE) population activity was recorded extracellularly. The results were consistent in showing that neither mefloquine (25 μM) nor genetic knockdown of Cx36 expression had anticonvulsant effects on SLE activity generated by either method. These findings call into question the widely held idea that open Cx36 gap junctions promote seizure activity.