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.
Binder
Devin K
DK
Department of Neurological Surgery, University of California, San Francisco, 94110, USA.
Yao
Xiaoming
X
Zador
Zsolt
Z
Sick
Thomas J
TJ
Verkman
Alan S
AS
Manley
Geoffrey T
GT
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