Neurotoxicity of channel mutations in heterologously expressed α7-nicotinic acetylcholine receptors
| Autor: | Elzbieta Puchacz, Linda Lucero, Jean Luc Galzi, John D. Fryer, Daniel Bertrand, Ronald J. Lukas, Bruno Buisson, Jean-Pierre Changeux |
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| Rok vydání: | 2001 |
| Předmět: |
Methyllycaconitine
Agonist medicine.drug_class musculoskeletal neural and ocular physiology General Neuroscience Mutant Transfection Biology complex mixtures Molecular biology chemistry.chemical_compound Nicotinic agonist nervous system chemistry Downregulation and upregulation Competitive antagonist medicine sense organs psychological phenomena and processes Acetylcholine receptor |
| Zdroj: | European Journal of Neuroscience. 13:1849-1860 |
| ISSN: | 0953-816X |
| Popis: | Nicotinic acetylcholine receptors (nAChR) composed of chick alpha7 subunits mutated to threonine at amino acid valine-251 in the putative channel-lining M2 domain were expressed heterologously in several neuron-like and non-neuronal mammalian cell lines. Expression of mutant alpha7-nAChR is toxic to neuron-like cells of the human neuroblastoma cell lines SH-SY5Y and IMR-32, but not to several other cell types. Growth in the presence of the alpha7-nAChR antagonist methyllycaconitine (MLA) protects against neurotoxicity, as does gradual downregulation of functional, mutant alpha7-nAChR in surviving transfected SH-SY5Y cells. Relative to wild-type alpha7-nAChR, functional alpha7-nAChR mutants show a higher affinity for agonists, slower rates of desensitization, and sensitivity to dihydro-beta-erythroidine (DHbetaE) as an agonist, but they retain sensitivity to MLA as a competitive antagonist. These findings demonstrate that expression of hyperfunctional, mutant forms of Ca2+-permeable alpha7-nAChR is toxic to neuron-like cells. |
| Databáze: | OpenAIRE |
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