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

Devin K. Binder, Xiaoming Yao, Zsolt Zador, Thomas Sick, Alan S. Verkman, Geoffrey T. Manley

Research output: Contribution to journalArticle

232 Scopus citations

Abstract

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 μA 114 ± 10 μA). 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 ± 0.5 s) as well as the recovery to baseline [K+]o (t1/2, 15.6 ± 1.5 s) were slowed in AQP4 -/- mice compared to WT mice (t1/2, 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.

Original languageEnglish
Pages (from-to)631-636
Number of pages6
JournalGLIA
Volume53
Issue number6
DOIs
StatePublished - Apr 15 2006

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Keywords

  • Aquaporin
  • Astrocyte
  • Epilepsy
  • Extracellular space
  • Glial cell
  • Potassium
  • Seizure

ASJC Scopus subject areas

  • Immunology

Cite this

Binder, D. K., Yao, X., Zador, Z., Sick, T., Verkman, A. S., & Manley, G. T. (2006). Increased seizure duration and slowed potassium kinetics in mice lacking aquaporin-4 water channels. GLIA, 53(6), 631-636. https://doi.org/10.1002/glia.20318