The effect of amyotrophic lateral sclerosis-linked exogenous SOD1-G93A on electrophysiological properties and intracellular calcium in cultured rat astrocytes
| Autor: | Ljiljana Nikolić, Milena Milosevic, Pavle R. Andjus, Dunja Bijelić, Danijela Bataveljic |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Time Factors Membrane permeability SOD1 Biophysics chemistry.chemical_element Biology Calcium Calcium in biology Membrane Potentials Superoxide dismutase 03 medical and health sciences Cytosol 0302 clinical medicine Calcium imaging medicine Animals Humans Rats Wistar Cells Cultured Cerebral Cortex Membrane potential Superoxide Dismutase nutritional and metabolic diseases Molecular biology Electric Stimulation Rats Cell biology 030104 developmental biology medicine.anatomical_structure Animals Newborn Neurology chemistry Astrocytes Mutation biology.protein Neurology (clinical) 030217 neurology & neurosurgery Astrocyte |
| Zdroj: | Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. 17:443-451 |
| ISSN: | 2167-9223 2167-8421 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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