Upregulation Of Connexin 32 In Hippocampus Of Pentylenetetrazole Kindling Rats And The Protective Effects Of Carbenoxolone

ObjectionsGap junctions are intercellular transmembrane channels, which facilitate ionic homeostasis and synchronization of action potentials in the nervous system. There is now increasing evidence implicating a role for gap junctions in the development of the synchronization of neuronal discharges characteristic of seizure disorders. The aqueous pores of gap junctions are formed by docking of two hemichannels, each comprised of six connexin (CX) protein subunits that permit the passage of ions, metabolites and second messenger molecules (<1.2 kDa), thereby providing a pathway for both electrical and chemical communication between coupled cells. Among all of the connexin subunits, CX32 is most widespread in neuron. Carbenoxolone, as an antiulcer medicine, was found can inhibit gap junctional intercellular communication. Carbenoxolone have been shown to depress epileptiform activity in vitro studies. Therefore, this study investigated whether CX32 is elevated in hippocampus and the gap junction blocker carbenoxolone can inhibit seizure development in pentylenetetrazole kindling rats.MethodsThe kindling model was induced by intraperitoneal injection of pentylenetetrazole (35mg/kg) every 48 hours for 10 times. Carbenoxolone were intraperitoneal administered (10mg/kg or 20mg/kg) 1 hour before above injection. The rates and the latency of seizure were observed. Two weeks after the last seizure, the bilateral hippocampus were taken and the level of CX32 was measured by western blot technique.ResultsMost of the rats were kindled before the tenth intraperitoneal injection of pentylenetetrazole. Carbenoxolone with 20mg/kg decreased the seizure rates and prolonged the latency of seizure significantly (P<0.01) , although carbenoxolone with 10mg/kg only prolonged the latency of seizure. The expression of CX32 was increased significantly in kindling rats compared with the controls (P<0.05). However, the expression of CX32 was not changed in rats administed with 20mg/kg carbenoxolone.ConclusionsIt suggests that CX32 and gap junctions might be involved in the development of epileptiform activity. Gap junction blocker carbenoxolone might play a certain protective role in seizure development.