Neurotoxicity of channel mutations in heterologously expressed α7-nicotinic acetylcholine receptors

Ronald J. Lukas, Linda Lucero, Bruno Buisson, Jean Luc Galzi, Elzbieta Puchacz, John D. Fryer, Jean Pierre Changeux, Daniel Bertrand

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1849-1860
Number of pages12
JournalEuropean Journal of Neuroscience
Issue number10
StatePublished - 2001


  • Chick
  • Human
  • Neuronal cell death
  • Nicotine
  • α-Bungarotoxin

ASJC Scopus subject areas

  • Neuroscience(all)


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