title: The effect of amyotrophic lateral sclerosis-linked exogenous SOD1-G93A on electrophysiological properties and intracellular calcium in cultured rat astrocytes.
abstract: Over 150 mutations in the SOD1 gene that encodes Cu/Zn superoxide dismutase (SOD1) cause 20-25% of familial ALS, albeit without a known gain-of-function mechanism. ALS is also non-cell-autonomous, the interactions between motor neurons and their glial neighbours being implicated in disease progression. The aim here was to investigate the biophysical effects of the exogenous human mutant SOD1-G93A on rat astrocytes in culture. Primary cortical astrocyte cultures were treated with recombinant human apo- mSOD1-G93A vs. wild-type control (wtSOD1) and recorded by patch-clamp and calcium imaging. Results showed that exogenous mSOD1 as well as wtSOD1 induced a decrease of membrane resistance, the effect being persistent (up to 13 min) only for the mutant form. Similarly, whole-cell inward currents in astrocytes were augmented by both wt and mSOD1, but the effect was twice larger and only progressed continuously for the latter. Both forms of SOD1 also induced a rise in intracellular Ca(2+) activity, the effect being dependent on external Ca(2+) and again only persisted with mSOD1, becoming significantly different from wtSOD1 only at longer times (14 min). In conclusion, this study points to membrane permeability and Ca(2+) signalling as processes affected by SOD1-G93A that presents the humoral factor triggering the role of astrocytes in ALS pathophysiology.
authors.affiliation: a Centre for Laser Microscopy , Faculty of Biology University of Belgrade , Studentski trg 3 and.
authors.forename: Milena
authors.initials: M
authors.lastname: Milošević
authors.affiliation: a Centre for Laser Microscopy , Faculty of Biology University of Belgrade , Studentski trg 3 and.
authors.forename: Danijela
authors.initials: D
authors.lastname: Bataveljić
authors.affiliation: b Department of Neurophysiology , Institute for Biological Research 'Siniša Stanković' University of Belgrade , Belgrade , Serbia.
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Nikolić
authors.affiliation: a Centre for Laser Microscopy , Faculty of Biology University of Belgrade , Studentski trg 3 and.
authors.forename: Dunja
authors.initials: D
authors.lastname: Bijelić
authors.affiliation: a Centre for Laser Microscopy , Faculty of Biology University of Belgrade , Studentski trg 3 and.
authors.forename: Pavle
authors.initials: P
authors.lastname: Andjus
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology*; D001703:Biophysics; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003600:Cytosol / Q000187:drug effects* / Q000378:metabolism; D004558:Electric Stimulation; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects*; D009154:Mutation / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000235:genetics / Q000494:pharmacology*; D013997:Time Factors
chemical_list: C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D002118:Calcium
keywords: ALS; Ca2+ imaging; cultured astrocytes; exogenous superoxide dismutase; membrane resistance; transmembrane currents