Mutations in the channel domain of a neuronal nicotinic receptor convert ion selectivity from cationic to anionic

Nature. 1992 Oct 8;359(6395):500-5. doi: 10.1038/359500a0.

Abstract

Introduction by site-directed mutagenesis of three amino acids from the MII segment of glycine or gamma-aminobutyric acid (GABAA) receptors into the MII segment of alpha 7 nicotinic receptor was sufficient to convert a cation-selective channel into an anion-selective channel gated by acetylcholine. A critical mutation was the insertion of an uncharged residue at the amino-terminal end of MII, stressing the importance of protein geometrical constraints on ion selectivity.

Publication types

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

MeSH terms

  • Acetylcholine / pharmacology
  • Amino Acid Sequence
  • Animals
  • Anions
  • Calcium
  • Cations
  • Chelating Agents / pharmacology
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Ion Channel Gating / drug effects
  • Ion Channels / chemistry
  • Ion Channels / metabolism*
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed*
  • Neurons / chemistry*
  • Oocytes / metabolism
  • Permeability
  • Receptors, GABA-A / chemistry
  • Receptors, Glycine
  • Receptors, Neurotransmitter / chemistry
  • Receptors, Nicotinic / chemistry
  • Receptors, Nicotinic / genetics*
  • Receptors, Nicotinic / metabolism
  • Sequence Homology, Amino Acid
  • Structure-Activity Relationship
  • Xenopus

Substances

  • Anions
  • Cations
  • Chelating Agents
  • Ion Channels
  • Receptors, GABA-A
  • Receptors, Glycine
  • Receptors, Neurotransmitter
  • Receptors, Nicotinic
  • Egtazic Acid
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Acetylcholine
  • Calcium