title: Expression of sodium channel α subunits 1.1, 1.2 and 1.6 in rat hippocampus after kainic acid-induced epilepsy.
abstract: Voltage-gated Na(+) channels control neuronal excitability and are the primary target for the majority of anti-epileptic drugs. This study investigates the (sub)cellular expression patterns of three important brain-associated Na(+) channel α subunits: NaV1.1, NaV1.2 and NaV1.6 during epileptogenesis (induced by kainic acid) using time points that cover the period from induction to the chronic phase of epilepsy. NaV1.1 immunoreactivity was persistently reduced at 1 day, 3 weeks and 2 months after SE in CA1 and CA3. About 50% of the NaV1.1-positive interneurons was lost at one day after SE in all regions investigated. In the hilus a similar reduction in NeuN-positive neurons was found, while in the CA1 and CA3 region the loss in NeuN-positive neurons only reached 15% in the chronic phase of epilepsy. This implies a stronger shift in the balance between excitation and inhibition toward excitation in the CA1 and CA3 region than in the hilus. NaV1.2 immunoreactivity in the inner molecular layer of the dentate gyrus was lower than control at 1 day after SE. It increased at 3 weeks and 2 months after SE in the inner molecular layer and overlapped with sprouted mossy fibers. NaV1.6 immunoreactivity in the dendritic region of CA1 and CA3 was persistently reduced at all time-points during epileptogenesis. Some astrocytes expressed NaV1.1 and NaV1.6 at 3 weeks after SE. Expression data alone are not sufficient to explain changes in network stability, or infer causality in epileptogenesis. These results demonstrate that hippocampal sub-regional expression of NaV1.1, NaV1.2 and NaV1.6 Na(+) channel α subunits is altered during epileptogenesis in a time and location specific way. This implies that understanding epileptogenesis has to take into account several distinct and type-specific changes in sodium channel expression.
authors.affiliation: Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Xin
authors.initials: X
authors.lastname: Qiao
authors.forename: Taco R
authors.initials: TR
authors.lastname: Werkman
authors.forename: Jan A
authors.initials: JA
authors.lastname: Gorter
authors.forename: Wytse J
authors.initials: WJ
authors.lastname: Wadman
authors.forename: Erwin A
authors.initials: EA
authors.lastname: van Vliet
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism; D056654:CA3 Region, Hippocampal / Q000378:metabolism; D003292:Convulsants; D003627:Data Interpretation, Statistical; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000187:drug effects; D004827:Epilepsy / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D018690:Excitatory Amino Acid Agonists; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D007395:Interneurons / Q000378:metabolism; D007608:Kainic Acid; D008297:Male; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000096:biosynthesis* / Q000187:drug effects; D062551:NAV1.2 Voltage-Gated Sodium Channel / Q000096:biosynthesis* / Q000187:drug effects; D062557:NAV1.6 Voltage-Gated Sodium Channel / Q000096:biosynthesis* / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000503:physiopathology; D013226:Status Epilepticus / Q000139:chemically induced / Q000503:physiopathology
chemical_list: D003292:Convulsants; D018690:Excitatory Amino Acid Agonists; D062550:NAV1.1 Voltage-Gated Sodium Channel; D062551:NAV1.2 Voltage-Gated Sodium Channel; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568250:Scn1a protein, rat; C568253:Scn2A protein, rat; C507811:Scn8a protein, rat; D007608:Kainic Acid
keywords: Epileptogenesis; Mossy fiber sprouting; Status epilepticus; Temporal lobe epilepsy