title: Compensatory reduction of Cav3.1 expression in thalamocortical neurons of juvenile rats of WAG/Rij model of absence epilepsy.
abstract: Absence seizures are the non-convulsive form of generalized epilepsy critically dependent on T-type calcium channels (Cav3) in thalamic neurons. In humans, absences accompany only childhood or adolescent epileptic syndromes--though in its polygenic rat models WAG/Rij and GAERS the opposite developmental pattern is observed. Hereby we address this issue by transcriptional and functional study of thalamic Cav3 in juvenile (i.e., free of seizures) rats of the absence-prone WAG/Rij strain and their coevals of the maternal Wistar strain. First, we measured the low voltage-activated (LVA) Ca(2+) current in freshly isolated thalamocortical neurons from laterodorsal nucleus of thalamus. The difference between current densities in control (12.9 ± 1.8pA/pF) and absence epilepsy (7.9 ± 1.8pA/pF) groups reached ∼ 39%. Second, we assessed the contribution of different T-channel isoforms into the reduction of Cav3-mediated current in WAG/Rij juveniles by means of RT PCR. The expression of all three LVA calcium channels was revealed with the prevalence of G and I isoforms. The expression level of G isoform (Cav3.1) was 35% smaller in WAG/Rij strain if compared to the control animals while that of H and I isoforms (Cav3.2 and Cav3.3, respectively) remained stable. The weakened expression of Cav3.1 in juveniles of WAG/Rij rats could represent a compensatory mechanism determining the pattern of the age dependency in the disease manifestation by this model of absence epilepsy.
authors.affiliation: Department of Nerve & Muscle Physiology, Bogomoletz Institute of Physiology, NASU, Bogomotetz Str., 4, Kiev, 01024, Ukraine; International Center of Molecular Physiology, NASU, Kyiv, Ukraine; State Key Laboratory of Molecular and Cellular Physiology, Kyiv, Ukraine. Electronic address: sharopov@biph.kiev.ua.
authors.forename: Bizhan R
authors.initials: BR
authors.lastname: Sharop
authors.affiliation: Department of Nerve & Muscle Physiology, Bogomoletz Institute of Physiology, NASU, Bogomotetz Str., 4, Kiev, 01024, Ukraine; International Center of Molecular Physiology, NASU, Kyiv, Ukraine; State Key Laboratory of Molecular and Cellular Physiology, Kyiv, Ukraine.
authors.forename: Oleksii I
authors.initials: OI
authors.lastname: Boldyriev
authors.affiliation: International Center of Molecular Physiology, NASU, Kyiv, Ukraine; State Key Laboratory of Molecular and Cellular Physiology, Kyiv, Ukraine.
authors.forename: Mykhailo Y
authors.initials: MY
authors.lastname: Batiuk
authors.affiliation: Department of Nerve & Muscle Physiology, Bogomoletz Institute of Physiology, NASU, Bogomotetz Str., 4, Kiev, 01024, Ukraine.
authors.forename: Nataliia L
authors.initials: NL
authors.lastname: Shtefan
authors.affiliation: Department of Nerve & Muscle Physiology, Bogomoletz Institute of Physiology, NASU, Bogomotetz Str., 4, Kiev, 01024, Ukraine; International Center of Molecular Physiology, NASU, Kyiv, Ukraine; State Key Laboratory of Molecular and Cellular Physiology, Kyiv, Ukraine.
authors.forename: Yaroslav M
authors.initials: YM
authors.lastname: Shuba
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004832:Epilepsy, Absence / Q000473:pathology / Q000503:physiopathology*; D008564:Membrane Potentials / Q000502:physiology; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D016133:Polymerase Chain Reaction; D062706:Prodromal Symptoms; D017208:Rats, Wistar; D013788:Thalamus / Q000473:pathology / Q000503:physiopathology*; D046509:Tissue Culture Techniques
chemical_list: C500994:Cacna1g protein, rat; C509958:Cacna1h protein, rat; C583277:Cacna1i protein, rat; D020747:Calcium Channels, T-Type; D002118:Calcium
keywords: Absence epilepsy; Patch clamp; RT PCR; T-type calcium channels; Thalamus; WAG/Rij