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 wild-type than AQP4 mice. These results suggest that glial water channels may modulate brain excitability and the initiation and generalization of seizure activity.
Binder
Devin K
DK
Department of Neurological Surgery, University of California, 505 Parnassus Ave, Box 0112, San Francisco, CA 94143, USA.
Oshio
Kotaro
K
Ma
Tonghui
T
Verkman
A S
AS
Manley
Geoffrey T
GT
D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000818:Animals; D051401:Aquaporin 4; D020346:Aquaporins / Q000172:deficiency* / Q000235:genetics; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D001929:Brain Edema / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D003292:Convulsants / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D004827:Epilepsy / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010433:Pentylenetetrazole / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics*
C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D020346:Aquaporins; D003292:Convulsants; D010433:Pentylenetetrazole