title: Altered Sodium and Potassium, but not Calcium Currents in Cerebellar Granule Cells in an In Vitro Model of Neuronal Injury.
abstract: Acute injury of central nervous system (CNS) starts a cascade of morphological, molecular, and functional changes including formation of a fibrotic scar, expression of transforming growth factor beta 1 (TGF-β1), and expression of extracellular matrix proteins leading to arrested neurite outgrowth and failed regeneration. We assessed alteration of electrophysiological properties of cerebellar granule cells (CGCs) in two in vitro models of neuronal injury: (i) model of fibrotic scar created from coculture of meningeal fibroblasts and cerebral astrocytes with addition of TGF-β1; (ii) a simplified model based on administration of TGF-β1 to CGCs culture. Both models reproduced suppression of neurite outgrowth caused by neuronal injury, which was equally restored by chondroitinase ABC (ChABC), a key disruptor of fibrotic scar formation. Voltage-dependent calcium current was not affected in either injury model. However, intracellular calcium concentration could be altered as an expression of inositol trisphosphate receptor type 1 was suppressed by TGF-β1 and restored by ChABC. Voltage-dependent sodium current was significantly suppressed in CGCs cultured on a model of fibrotic scar and was only partly restored by ChABC. Administration of TGF-β1 significantly shifted current-voltage relation of sodium current toward more positive membrane potential without change to maximal current amplitude. Both transient and sustained potassium currents were significantly suppressed on a fibrotic scar and restored by ChABC to their control amplitudes. In contrast, TGF-β1 itself significantly upregulated transient and did not change sustained potassium current. Observed changes of voltage-dependent ion currents may contribute to known morphological and functional changes in injured CNS.
authors: Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Dubravska cesta 9, 84005, Bratislava, Slovakia.
authors: Katarína
authors: K
authors: Ondáčová
authors: KRD molecular technologies s. r. o, Saratovska 26, 84201, Bratislava, Slovakia.
authors: Dana
authors: D
authors: Jurkovičová
authors: Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Dubravska cesta 9, 84005, Bratislava, Slovakia. lubica.lacinova@savba.sk.
authors: Ľubica
authors: http://orcid.org/0000-0001-9207-0978
authors: Ľ
authors: Lacinová
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D002531:Cerebellum / Q000473:pathology*; D005355:Fibrosis; D005786:Gene Expression Regulation / Q000187:drug effects; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D008954:Models, Biological; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D015221:Potassium Channels / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D015222:Sodium Channels / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D015221:Potassium Channels; D012333:RNA, Messenger; D015222:Sodium Channels; D053773:Transforming Growth Factor beta1
keywords: Calcium current; Cerebellar granule cells; Chondroitinase ABC; Fibrotic scar; Potassium current; Sodium current; TGF-β1