Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

J. Physiol. 591 (4): 753-764


review-article

Ion channels in genetic and acquired forms of epilepsy

Holger Lerche1, Mala Shah2, Heinz Beck3, Jeff Noebels4, Dan Johnston5, and Angela Vincent6

1Department of Neurology and Epileptology, Hertie Institute of Clinical Brain Research, University of Tübingen, Hoppe-Seyler-Str. 3, D-72076 Tübingen, Germany2UCL School of Pharmacy, University College, London, WC1N 1AX, UK3Life and Brain Center, Experimental Epileptology and Cognition Research, University of Bonn Medical Center, Sigmund-Freud Str. 25, 53105 Bonn, Germany4Department of Neurology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA5Institute for Neuroscience, College of Natural Sciences, University of Texas at Austin, TX 78712, USA6Nuffield Department of Clinical Neurosciences, University of Oxford, Level 6, West Wing, John Radcliffe Hospital, Oxford OX3 9DU, UK

Abstract:

Abstract 
Genetic mutations causing dysfunction of both voltage- and ligand-gated ion channels make a major contribution to the cause of many different types of familial epilepsy. Key mechanisms comprise defective Na+ channels of inhibitory neurons, or GABAA receptors affecting pre- or postsynaptic GABAergic inhibition, or a dysfunction of different types of channels at axon initial segments. Many of these ion channel mutations have been modelled in mice, which has largely contributed to the understanding of where and how the ion channel defects lead to neuronal hyperexcitability. Animal models of febrile seizures or mesial temporal epilepsy have shown that dendritic K+ channels, hyperpolarization-activated cation channels and T-type Ca2+ channels play important roles in the generation of seizures. For the latter, it has been shown that suppression of their function by pharmacological mechanisms or in knock-out mice can antagonize epileptogenesis. Defects of ion channel function are also associated with forms of acquired epilepsy. Autoantibodies directed against ion channels or associated proteins, such as K+ channels, LGI1 or NMDA receptors, have been identified in epileptic disorders that can largely be included under the term limbic encephalitis which includes limbic seizures, status epilepticus and psychiatric symptoms. We conclude that ion channels and associated proteins are important players in different types of genetic and acquired epilepsies. Nevertheless, the molecular bases for most common forms of epilepsy are not yet clear, and evidence to be discussed indicates just how much more we need to understand about the complex mechanisms that underlie epileptogenesis.

A. Vincent: Nuffield Department of Clinical Neurosciences, University of Oxford, Level 6, West Wing, John Radcliffe Hospital, Oxford OX3 9DU, UK. Email: angela.vincent{at}ndcn.ox.ac.uk


The report was presented at the symposium Why do some brains seize? Molecular, cellular and network mechanisms, which took place at the Epilepsy Research UK Expert International Workshop, Oxford, UK on 15–16 March 2012.

(Received 8 July 2012; accepted after revision 21 October 2012; first published online 22 October 2012)

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Why do some brains seize? Molecular, cellular and network mechanisms.
A. Trevelyan (2013)
J. Physiol. 591, 751-752
   Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882