Increased seizure threshold in mice lacking aquaporin-4 water channels

Mice deficient in the glial water channel aquaporin-4 (AQP4) show decreased cerebral edema and improved neurological outcome following water intoxication or ischemic challenge. In this report, we tested seizure susceptibility in AQP4(-/-) mice. AQP4(-/-) mice and wild-type controls were given the chemoconvulsant pentylenetetrazol (PTZ) and monitored for seizure activity. At 40 mg/kg PTZ, all wild-type mice exhibited seizure activity, whereas six of seven AQP4(-/-) mice did not exhibit seizure activity. At 50 mg/kg PTZ, both groups exhibited seizure activity; however, the latency to generalized (tonic-clonic) seizures was significantly lower in wildtype than AQP4(-/-) mice. These results suggest that glial water channels may modulate brain excitability and the initiation and generalization of seizure activity.