Alteration of ionic selectivity of a K+ channel by mutation of the H5 region

Nature. 1991 Feb 21;349(6311):700-4. doi: 10.1038/349700a0.


The high ionic selectivity of K+ channels is a unifying feature of this diverse class of membrane proteins. Though K+ channels differ widely in regulation and kinetics, physiological studies have suggested a common structure: a single file pore containing multiple ion-binding sites and having broader vestibules at both ends. We have used site-directed mutagenesis and single-channel recordings to identify a molecular region that influences ionic selectivity in a cloned A-type K+ channel from Drosophila. Single amino-acid substitutions in H5, the fifth hydrophobic region, enhanced the passage of NH4+ and Rb+, ions with diameters larger than K+, without compromising the ability of the channel to exclude the smaller cation, Na+. The mutations that substantially altered selectivity had little effect on the gating properties of the channel. We conclude that the H5 region is likely to line the pore of the K+ channel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Ammonia / metabolism
  • Animals
  • Drosophila melanogaster
  • Electric Conductivity / drug effects
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Oocytes / metabolism
  • Potassium / metabolism
  • Potassium Channels / chemistry*
  • Potassium Channels / drug effects
  • Potassium Channels / genetics
  • Rubidium / metabolism
  • Sodium / metabolism
  • Structure-Activity Relationship
  • Tetraethylammonium
  • Tetraethylammonium Compounds / pharmacology
  • Xenopus laevis


  • Potassium Channels
  • Tetraethylammonium Compounds
  • Tetraethylammonium
  • Ammonia
  • Sodium
  • Rubidium
  • Potassium