Sodium and potassium competition in potassium-selective and non-selective channels.
Potassium channels selectively conduct K(+), primarily to the exclusion of Na(+), despite the fact that both ions can bind within the selectivity filter. Here we perform crystallographic titration and single-channel electrophysiology to examine the competition of Na(+) and K(+) binding within the filter of two NaK channel mutants; one is the potassium-selective NaK2K mutant and the other is the non-selective NaK2CNG, a CNG channel pore mimic. With high-resolution structures of these engineered NaK channel constructs, we explicitly describe the changes in K(+) occupancy within the filter upon Na(+) competition by anomalous diffraction. Our results demonstrate that the non-selective NaK2CNG still retains a K(+)-selective site at equilibrium, whereas the NaK2K channel filter maintains two high-affinity K(+) sites. A double-barrier mechanism is proposed to explain K(+) channel selectivity at low K(+) concentrations.
1] Department of Physiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9040, USA [2].
David B
DB
Sauer
Weizhong
W
Zeng
John
J
Canty
Yeeling
Y
Lam
Youxing
Y
Jiang
D001409:Bacillus cereus / Q000378:metabolism; D001412:Bacillus subtilis / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D001665:Binding Sites; D001667:Binding, Competitive; D018360:Crystallography, X-Ray; D004594:Electrophysiology; D004926:Escherichia coli / Q000378:metabolism; D015640:Ion Channel Gating; D008081:Liposomes / Q000378:metabolism; D009154:Mutation; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D011487:Protein Conformation; D012964:Sodium / Q000378:metabolism*
D001426:Bacterial Proteins; D008081:Liposomes; D015221:Potassium Channels; D012964:Sodium; D011188:Potassium