The role of a single aspartate residue in ionic selectivity and block of a murine inward rectifier K+ channel Kir2.1.
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.
Abrams
C J
CJ
Department of Cell Physiology and Pharmacology, University of Leicester, UK.
Davies
N W
NW
Shelton
P A
PA
Stanfield
P R
PR
D000818:Animals; D001224:Aspartic Acid / Q000235:genetics / Q000378:metabolism*; D002586:Cesium / Q000378:metabolism / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D004594:Electrophysiology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D009154:Mutation; D018408:Patch-Clamp Techniques; D010539:Permeability; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D012413:Rubidium / Q000378:metabolism / Q000494:pharmacology
D015221:Potassium Channels; D002586:Cesium; D001224:Aspartic Acid; D004247:DNA; D012413:Rubidium