Abstract
Potassium channels allow the selective flux of K+ excluding the smaller, and more abundant in the extracellular solution, Na+ ions. Here we show that Shab is a typical K+ channel that excludes Na+ under bi-ionic, Nao/Ki or Nao/Rbi, conditions. However, when internal K+ is replaced by Cs+ (Nao/Csi), stable inward Na+ and outward Cs+ currents are observed. These currents show that Shab selectivity is not accounted for by protein structural elements alone, as implicit in the snug-fit model of selectivity. Additionally, here we report the block of Shab channels by external Ca2+ ions, and compare the effect that internal K+ replacement exerts on both Ca2+ and TEA block. Our observations indicate that Ca2+ blocks the channels at a site located near the external TEA binding site, and that this pore region changes conformation under conditions that allow Na+ permeation. In contrast, the latter ion conditions do not significantly affect the binding of quinidine to the pore central cavity. Based on our observations and the structural information derived from the NaK bacterial channel, we hypothesize that Ca2+ is probably coordinated by main chain carbonyls of the pore´s first K+-binding site.
Highlights
Potassium channels are proteins that allow the passive and selective flux of K+, excluding the smaller, and more abundant in the extracellular solution Na+ ions
K+ channels are defined by their common characteristic of being highly selective for K+ over Na+ ions
We demonstrate that the iso-osmollar replacement of intracellular K+ by Cs+ ions allows Shab channels to stably conduct both Cs+ and Na+ ions
Summary
Potassium channels are proteins that allow the passive and selective flux of K+, excluding the smaller, and more abundant in the extracellular solution Na+ ions. The structural framework of this selectivity resides in a conserved amino acid signature sequence (TVGYG) [1], which forms the selectivity filter (SF) of the pore [2,3,4]. Backbone carbonyl oxygen atoms from signature sequence residues point towards the pore lumen, simultaneously coordinating up to two dehydrated K+ ions at alternate positions, or binding sites (s1/s3 or s2/s4) [3]. The above proposal corresponds to the “snug-fit” model of selectivity [5] This model does not assign any role to K+ ions themselves in the determination of selectivity, and according to it permeation of large ions, such as Cs+ (atomic radius = 1.69Ǻ), should be halted
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