title: Seizure-induced plasticity of h channels in entorhinal cortical layer III pyramidal neurons.
abstract: The entorhinal cortex (EC) provides the predominant excitatory drive to the hippocampal CA1 and subicular neurons in chronic epilepsy. Discerning the mechanisms underlying signal integration within EC neurons is essential for understanding network excitability alterations involving the hippocampus during epilepsy. Twenty-four hours following a single seizure episode when there were no behavioral or electrographic seizures, we found enhanced spontaneous activity still present in the rat EC in vivo and in vitro. The increased excitability was accompanied by a profound reduction in I(h) in EC layer III neurons and a significant decline in HCN1 and HCN2 subunits that encode for h channels. Consequently, dendritic excitability was enhanced, resulting in increased neuronal firing despite hyperpolarized membrane potentials. The loss of I(h) and the increased neuronal excitability persisted for 1 week following seizures. Our results suggest that dendritic I(h) plays an important role in determining the excitability of EC layer III neurons and their associated neural networks.
authors.affiliation: Division of Neuroscience, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Mala M
authors.initials: MM
authors.lastname: Shah
authors.forename: Anne E
authors.initials: AE
authors.lastname: Anderson
authors.forename: Victor
authors.initials: V
authors.lastname: Leung
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Lin
authors.forename: Daniel
authors.initials: D
authors.lastname: Johnston
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D015153:Blotting, Western / Q000379:methods; D054815:Cyclic Nucleotide-Gated Cation Channels; D003712:Dendrites / Q000187:drug effects / Q000502:physiology; D004569:Electroencephalography / Q000379:methods; D018728:Entorhinal Cortex / Q000473:pathology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D007608:Kainic Acid; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009124:Muscle Proteins / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D015221:Potassium Channels; D017966:Pyramidal Cells / Q000187:drug effects / Q000503:physiopathology*; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; D018690:Excitatory Amino Acid Agonists; D018756:GABA Antagonists; C578667:Hcn1 protein, rat; C578712:Hcn2 protein, rat; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D009124:Muscle Proteins; D015221:Potassium Channels; D011743:Pyrimidines; C082246:ICI D2788; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine; D007608:Kainic Acid; D001640:Bicuculline