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Focused Review ARTICLE

Double trouble? Potential for hyperexcitability following both channelopathic up- and downregulation of I_h in epilepsy

Jonas Dyhrfjeld-Johnsen^1,2*, Robert J. Morgan³ and Ivan Soltesz³

Harvard Medical School, Boston, MA, USA

Neurology, Massachusetts General Hospital, Boston, MA, USA

Anatomy and Neurobiology, University of California – Irvine, Irvine, CA, USA

Studies of pathological ion channel regulation as an underlying mechanism of epilepsy have revealed alterations in the h-current in several animal models. While earlier reports indicate that downregulation of the h-current is pro-excitatory on the single neuron level, we found an upregulation of I_h in hyperexcitable CA1 pyramidal neuron dendrites following experimental febrile seizures. In addition, in several CA1 pyramidal neuron computational models of different complexity, h-current upregulation has been shown to lead to pro-excitable effects. This focused review examines the complex impact of altered h-current on neuronal resting membrane potential (RMP) and input resistance (R_in), as well as reported interactions with other ionic conductances.

Keywords:

h-current, excitability, acquired channelopathy, epilepsy

Citation:

Dyhrfjeld-Johnsen J, Morgan RJ and Soltesz I (2009). Double trouble? Potential for hyperexcitability following both channelopathic up- and downregulation of I_h in epilepsy. Front. Neurosci. 3:1. doi: 10.3389/neuro.01.005.2009

Received:

01 February 2009;

Paper pending published:

19 February 2009;

Accepted:

04 March 2009;

Published online:

01 May 2009.

Edited by:

Alexander Borst, Max Planck Institute of Neurobiology, Germany

Reviewed by:

Nelson Spruston, Northwestern University, USA
Valentin Stein, Max Planck Institute of Neurobiology, Germany

© 2009 Dyhrfjeld-Johnsen, Morgan and Soltesz. This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.

*Correspondence:

Dr. Jonas Dyhrfjeld-Johnsen, MGH Neurology, CNY B-114, Rm. 2502, 16th Street, Charlestown, MA 02129, USA, e-mail: jdyhrfjeld-johnsen@partners.org