Brain Water and Ion Fluxes: A Hard-to-Die Hypothesis to Explain Seizures

Abstract

Increased Seizure Duration and Slowed Potassium Kinetics in Mice Lacking Aquaporin-4 Water Channels. Binder DK, Yao X, Zador Z, Sick TJ, Verkman AS, Manley GT. Glia 2006;53:631–636. 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 μ 2 s vs. 13 μ 2 s). In addition, AQP4 -/- mice were found to have a higher seizure threshold (167 μ 17 A vs. 114 μ 10 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 ( t1/2, 2.3 μ 0.5 s) as well as the recovery to baseline [K+]o ( t1/2, 15.6 μ 1.5 s) were slowed in AQP4 -/- mice compared to WT mice ( t1/2, 0.5 μ 0.1 and 6.6 μ 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.