Baram, TZ

Bender, RA

Brewster, AL

Mathern, GW

eScholarship - University of California

UC IrvineUC Irvine Previously Published WorksTitleThe hyperpolarization-activated HCN channels in human and experimental hippocampal epilepsy: A novel, acquired channelopathy?Permalinkhttps://escholarship.org/uc/item/3fb838v3JournalANNALS OF NEUROLOGY, 54ISSN0364-5134AuthorsBender, RAMathern, GWBrewster, ALet al.Publication Date2003Copyright InformationThis work is made available under the terms of a Creative Commons Attribution License, availalbe at https://creativecommons.org/licenses/by/4.0/ Peer reviewedeScholarship.org Powered by the California Digital LibraryUniversity of CaliforniaS54 Annals of Neurology Vol 54 (suppl 7) 2003 139. The Hyperpolarization-Activated HCN Channelsin Human and Experimental Hippocampal Epilepsy: ANovel, Acquired Channelopathy�Roland A. Bender, Gary W. Mathern, Amy L. Brewster, andTallie Z. Baram; Irvine and Los Angeles, C4Changes in ion channel expression, influencing neuronal ex­citability, are emerging as contributory mechanisms in hu­man epilepsies. Previously, we found isoform-specific altered expression of hyperpolarization-activated cAMP-gated chan­nels (HCNs), correlating with long-term hippocampal hyper­excitability, in immature rat model of prolonged febrile sei­zures (PFSs). PFSs commonly precede temporal lobe epilepsy (TLE), suggesting that transcriptional HCN dysregulation might contribute to the epileptogenic process. Therefore, we analyzed HCN expression in TLE hippocampus. HCN1&2 mRNA and protein expression were measured in three hip­pocampi groups: TLE+hippocampal sclerosis (HS; n = 17), TLE without HS (NHS; n = 10); and autopsies (n = 10). In autopsy and NHS, HCNlmRNA expression was robust in pyramidal cell layers and lower in granule cells (GCs). However, HCNlmRNA increased drastically in GCs from epileptic hippocampus once GC density was reduced by greater than 50%. Increased HCNl immunoreactivity in GC dendritic fields accompanied these mRNA changes, whereas HCN2mRNA changes were modest. Thus, HCN expression is dynamically regulated in TLE. After experimental PFS (early in epileptogenesis), preserved, augmented inhibition may reduce HCNl levels. Conversely, in chronic TLE+HS, hilar cell loss and consequent reduced inhibition, coupled with increased dendritic excitation of surviving GCs, might enhance "compensatory" HCNl expression. Supported by NIH, NINOS NS35439 (T.Z.B.) and NS28912 (A.LB., T.Z.B.), NS02808 and NS38992 (G.W.M.), and by an Ep­ilepsy Foundation of America, Milken Foundation postdoc­toral research fellowship (R.A.B.). Program and Abstracts, American Neurological Association S55 

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The hyperpolarization-activated HCN channels in human and experimental hippocampal epilepsy: A novel, acquired channelopathy?

https://escholarship.org/content/qt3fb838v3/qt3fb838v3.pdf?t=pysyx7

The hyperpolarization-activated HCN channels in human and experimental hippocampal epilepsy: A novel, acquired channelopathy?

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