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Potential role of the glial water channel aquaporin-4 in epilepsy

Published online by Cambridge University Press:  03 June 2008

Mike S. Hsu
Affiliation:
Epilepsy Research Laboratory, Department of Neurological Surgery, University of California, Irvine, USA
Darrin J. Lee
Affiliation:
Epilepsy Research Laboratory, Department of Neurological Surgery, University of California, Irvine, USA
Devin K. Binder
Affiliation:
Epilepsy Research Laboratory, Department of Neurological Surgery, University of California, Irvine, USA

Abstract

Recent studies have implicated glial cells in novel physiological roles in the CNS, such as modulation of synaptic transmission, so it is possible that glial cells might have a functional role in the hyperexcitability that is characteristic of epilepsy. Indeed, alterations in distinct astrocyte membrane channels, receptors and transporters have all been associated with the epileptic state. This paper focuses on the potential roles of the glial water channel aquaporin-4 (AQP4) in modulating brain excitability and in epilepsy. We review studies of seizure phenotypes, K+ homeostasis and extracellular space physiology of mice that lack AQP4 (AQP4−/− mice) and discuss the human studies demonstrating alterations of AQP4 in specimens of human epilepsy tissue. We conclude with new studies of AQP4 regulation by seizures and discuss its potential role in the development of epilepsy (epileptogenesis). Although many questions remain unanswered, the available data indicate that AQP4 and its molecular partners might represent important new therapeutic targets.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2008

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