Paradoxical allosteric effects of competitive inhibitors on neuronal alpha7 nicotinic receptor mutants

Neuroreport. 1997 Nov 10;8(16):3591-6. doi: 10.1097/00001756-199711100-00034.


Mutation of the conserved leucine residue, in the second transmembrane domain of the neuronal alpha7 acetylcholine receptor to a threonine (L247T) causes pleiotropic alterations of receptor properties. In this study we examined the effects of competitive inhibitors on the alpha7-L247T physiological responses. While the alpha7 competitive inhibitor dihydro-beta-erythroidine evoked a current comparable to that induced by ACh, other inhibitors such as methyllycaconitine (MLA) and alpha-bungarotoxin (alpha-Bgt) caused a blockade of alpha7-L247T to ACh activation. When applied in the absence of ACh, MLA or alpha-Bgt reduced the cell leakage current, showing that alpha7-L247T displays a significant fraction (10%) of spontaneously open channels. These data can be interpreted in terms of an allosteric model, assuming that the L247T mutant possesses a low isomerization constant L and that MLA and alpha-Bgt stabilize the closed, resting state.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology*
  • Aconitine / analogs & derivatives
  • Aconitine / pharmacology
  • Allosteric Regulation
  • Amino Acid Substitution
  • Animals
  • Binding, Competitive
  • Bungarotoxins / pharmacology*
  • Dihydro-beta-Erythroidine / pharmacology
  • Evoked Potentials / drug effects
  • Leucine
  • Mutagenesis, Site-Directed
  • Neurons / physiology*
  • Oocytes / physiology
  • Receptors, Nicotinic / biosynthesis
  • Receptors, Nicotinic / chemistry
  • Receptors, Nicotinic / physiology*
  • Recombinant Proteins / biosynthesis
  • Xenopus
  • alpha7 Nicotinic Acetylcholine Receptor


  • Bungarotoxins
  • Receptors, Nicotinic
  • Recombinant Proteins
  • alpha7 Nicotinic Acetylcholine Receptor
  • methyllycaconitine
  • Dihydro-beta-Erythroidine
  • Leucine
  • Acetylcholine
  • Aconitine