Increased seizure duration and slowed potassium kinetics in mice lacking aquaporin-4 water channels

被引:297
作者
Binder, DK
Yao, XM
Zador, Z
Sick, TJ
Verkman, AS
Manley, GT
机构
[1] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94110 USA
[2] Univ Miami, Sch Med, Dept Neurol, Miami, FL 33152 USA
[3] Univ Calif San Francisco, Dept Med & Physiol, San Francisco, CA 94110 USA
关键词
aquaporin; astrocyte; epilepsy; extracellular space; glial cell; potassium; seizure;
D O I
10.1002/glia.20318
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 mu A vs. 114 +/- 10 mu A). 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), 0.3 +/- 0.5 s) as well as the recovery to baseline [K+](o), (t(1/2), 5.6 +/- 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. (c) 2006 Wiley-Liss, Inc.
引用
收藏
页码:631 / 636
页数:6
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