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

55 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.


  • Epilepsy
  • GABA
  • Glutamate
  • Glycogen
  • Potassium


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