ISSN:
1460-9568
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Nicotinic acetylcholine receptors (nAChR) composed of chick α7 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 α7-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 α7-nAChR antagonist methyllycaconitine (MLA) protects against neurotoxicity, as does gradual downregulation of functional, mutant α7-nAChR in surviving transfected SH-SY5Y cells. Relative to wild-type α7-nAChR, functional α7-nAChR mutants show a higher affinity for agonists, slower rates of desensitization, and sensitivity to dihydro-β-erythroidine (DHβE) 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 α7-nAChR is toxic to neuron-like cells.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.0953-816x.2001.01560.x
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