Increased seizure duration and slowed potassium kinetics in mice lacking aquaporin-4 water channels.
The glial water channel aquaporin-4 (AQP4) has been hypothesized to modulate water and potassium fluxes associated with neuronal activity. In this study, we examined the seizure phenotype of AQP4 -/- mice using in vivo electrical stimulation and electroencephalographic (EEG) recording. AQP4 -/- mice were found to have dramatically prolonged stimulation-evoked seizures after hippocampal stimulation compared to wild-type controls (33 +/- 2 s vs. 13 +/- 2 s). In addition, AQP4 -/- mice were found to have a higher seizure threshold (167 +/- 17 microA vs. 114 +/- 10 microA). To assess a potential effect of AQP4 on potassium kinetics, we used in vivo recording with potassium-sensitive microelectrodes after direct cortical stimulation. Although there was no significant difference in baseline or peak [K(+)](o), the rise time to peak [K(+)](o) (t(1/2), 2.3 +/- 0.5 s) as well as the recovery to baseline [K(+)](o) (t(1/2), 15.6 +/- 1.5 s) were slowed in AQP4 -/- mice compared to WT mice (t(1/2), 0.5 +/- 0.1 and 6.6 +/- 0.7 s, respectively). These results implicate AQP4 in the expression and termination of seizure activity and support the hypothesis that AQP4 is coupled to potassium homeostasis in vivo.
Department of Neurological Surgery, University of California, San Francisco, 94110, USA.
Devin K
DK
Binder
Xiaoming
X
Yao
Zsolt
Z
Zador
Thomas J
TJ
Sick
Alan S
AS
Verkman
Geoffrey T
GT
Manley
D000200:Action Potentials / Q000235:genetics; D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics*; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D001929:Brain Edema / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004569:Electroencephalography; D005110:Extracellular Space / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D006706:Homeostasis / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism; D012640:Seizures / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D015398:Signal Transduction / Q000235:genetics; D014883:Water-Electrolyte Imbalance / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology
C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D015221:Potassium Channels; D011188:Potassium