Physiological bases of the K+ and the glutamate/GABA hypotheses of epilepsy

Mauro DiNuzzo, Silvia Mangia, Bruno Maraviglia, Federico Giove

Research output: Contribution to journalReview articlepeer-review

36 Scopus citations


Epilepsy is a heterogeneous family of neurological disorders that manifest as seizures, i.e. the hypersynchronous activity of large population of neurons. About 30% of epileptic patients do not respond to currently available antiepileptic drugs. Decades of intense research have elucidated the involvement of a number of possible signaling pathways, however, at present we do not have a fundamental understanding of epileptogenesis. In this paper, we review the literature on epilepsy under a wide-angle perspective, a mandatory choice that responds to the recurrent and unanswered question about what is epiphenomenal and what is causal to the disease. While focusing on the involvement of K+ and glutamate/GABA in determining neuronal hyperexcitability, emphasis is given to astrocytic contribution to epileptogenesis, and especially to loss-of-function of astrocytic glutamine synthetase following reactive astrogliosis, a hallmark of epileptic syndromes. We finally introduce the potential involvement of abnormal glycogen synthesis induced by excess glutamate in increasing susceptibility to seizures.

Original languageEnglish (US)
Pages (from-to)995-1012
Number of pages18
JournalEpilepsy Research
Issue number6
StatePublished - Aug 2014

Bibliographical note

Funding Information:
The author S.M. thanks the grant KL2 RR033182 from the National Institute of Health (NIH) to the University of Minnesota Clinical and Translational Science Institute (CTSI) for support.

Copyright 2018 Elsevier B.V., All rights reserved.


  • Epilepsy
  • GABA
  • Glutamate
  • Glycogen
  • Potassium

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