The role of a single aspartate residue in ionic selectivity and block of a murine inward rectifier K+ channel Kir2.1

J Physiol. 1996 Jun 15;493 ( Pt 3)(Pt 3):643-9. doi: 10.1113/jphysiol.1996.sp021411.

Abstract

1. The effects of Rb+ and Cs+ as blocking ions were investigated on wild-type and mutant forms of the inward rectifier K+ channel, IRK1 (Kir2.1). 2. In wild-type channels, Rb+ blockage was voltage dependent, increasing and then falling with increasing hyperpolarization. 3. Rb+ blockage was abolished by replacing Asp172 in the M2 domain of the pore-forming subunit by Asn, but was re-established by a change to Gln, narrowing the pore. Blocking affinity was reduced in D172Q, and was also reduced by replacing Gly168 in M2 by Ala. 4. Cs+ blockage was also abolished in D172N but was re-established in D172Q. 5. There appears to be a balance between charge and pore size in determining whether ions block or permeate. A major part of the selectivity of Kir2.1 is associated with Asp172 in the M2 domain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aspartic Acid / genetics
  • Aspartic Acid / metabolism*
  • Cesium / metabolism
  • Cesium / pharmacology
  • DNA / biosynthesis
  • Electrophysiology
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology
  • Membrane Potentials / physiology
  • Mice
  • Mutation
  • Patch-Clamp Techniques
  • Permeability
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • Rubidium / metabolism
  • Rubidium / pharmacology

Substances

  • Potassium Channels
  • Cesium
  • Aspartic Acid
  • DNA
  • Rubidium