title: Regionally specific expression of high-voltage-activated calcium channels in thalamic nuclei of epileptic and non-epileptic rats.
abstract: The polygenic origin of generalized absence epilepsy results in dysfunction of ion channels that allows the switch from physiological asynchronous to pathophysiological highly synchronous network activity. Evidence from rat and mouse models of absence epilepsy indicates that altered Ca(2+) channel activity contributes to cellular and network alterations that lead to seizure activity. Under physiological circumstances, high voltage-activated (HVA) Ca(2+) channels are important in determining the thalamic firing profile. Here, we investigated a possible contribution of HVA channels to the epileptic phenotype using a rodent genetic model of absence epilepsy. In this study, HVA Ca(2+) currents were recorded from neurons of three different thalamic nuclei that are involved in both sensory signal transmission and rhythmic-synchronized activity during epileptic spike-and-wave discharges (SWD), namely the dorsal part of the lateral geniculate nucleus (dLGN), the ventrobasal thalamic complex (VB) and the reticular thalamic nucleus (NRT) of epileptic Wistar Albino Glaxo rats from Rijswijk (WAG/Rij) and non-epileptic August Copenhagen Irish (ACI) rats. HVA Ca(2+) current densities in dLGN neurons were significantly increased in epileptic rats compared with non-epileptic controls while other thalamic regions revealed no differences between the strains. Application of specific channel blockers revealed that the increased current was carried by L-type Ca(2+) channels. Electrophysiological evidence of increased L-type current correlated with up-regulated mRNA and protein expression of a particular L-type channel, namely Cav1.3, in dLGN of epileptic rats. No significant changes were found for other HVA Ca(2+) channels. Moreover, pharmacological inactivation of L-type Ca(2+) channels results in altered firing profiles of thalamocortical relay (TC) neurons from non-epileptic rather than from epileptic rats. While HVA Ca(2+) channels influence tonic and burst firing in ACI and WAG/Rij differently, it is discussed that increased Cav1.3 expression may indirectly contribute to increased robustness of burst firing and thereby the epileptic phenotype of absence epilepsy.
authors.affiliation: Institut für Physiologie I, Robert-Koch-Str. 27a, D-48149 Münster, Germany.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Kanyshkova
authors.affiliation: Institut für Physiologie I, Robert-Koch-Str. 27a, D-48149 Münster, Germany; Department für Neurologie, Klinik für Allgemeine Neurologie and Institut für Physiologie, Abteilung für Neuropathophysiologie, Albert-Schweitzer-Campus 1, Westfälische Wilhelms-Universität, D-48149 Münster, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Ehling
authors.affiliation: Institut für Physiologie I, Robert-Koch-Str. 27a, D-48149 Münster, Germany; Department für Neurologie, Klinik für Allgemeine Neurologie and Institut für Physiologie, Abteilung für Neuropathophysiologie, Albert-Schweitzer-Campus 1, Westfälische Wilhelms-Universität, D-48149 Münster, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Cerina
authors.affiliation: Institut für Physiologie I, Robert-Koch-Str. 27a, D-48149 Münster, Germany; Department für Neurologie, Klinik für Allgemeine Neurologie and Institut für Physiologie, Abteilung für Neuropathophysiologie, Albert-Schweitzer-Campus 1, Westfälische Wilhelms-Universität, D-48149 Münster, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Meuth
authors.affiliation: Institut für Physiologie I, Robert-Koch-Str. 27a, D-48149 Münster, Germany.
authors.forename: Mehrnoush
authors.initials: M
authors.lastname: Zobeiri
authors.affiliation: Department für Neurologie, Klinik für Allgemeine Neurologie and Institut für Physiologie, Abteilung für Neuropathophysiologie, Albert-Schweitzer-Campus 1, Westfälische Wilhelms-Universität, D-48149 Münster, Germany.
authors.forename: Sven G
authors.initials: SG
authors.lastname: Meuth
authors.affiliation: Institut für Physiologie I, Robert-Koch-Str. 27a, D-48149 Münster, Germany.
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Pape
authors.affiliation: Institut für Physiologie I, Robert-Koch-Str. 27a, D-48149 Münster, Germany. Electronic address: tbudde@uni-muenster.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Budde
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology; D000420:Albuterol / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D055592:Biophysical Phenomena / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004827:Epilepsy / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D059645:Mutation Rate; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D000068299:Salmeterol Xinafoate; D016559:Tacrolimus / Q000031:analogs & derivatives / Q000494:pharmacology; D013787:Thalamic Nuclei / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics / Q000502:physiology*
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007166:Immunosuppressive Agents; D009419:Nerve Tissue Proteins; D000068299:Salmeterol Xinafoate; C058028:immunomycin; D000420:Albuterol; D016559:Tacrolimus
keywords: Genetic rat model of absence epilepsy; HVA Ca(2+) channels; L-type Ca(2+) channels; Thalamus; Tonic firing