Potassium Versus Sodium Selectivity in Monovalent Ion Channel Selectivity Filters

Transport of Na(+) and K(+) ions across the cell membrane is carried out by specialized pore-forming ion channel proteins, which exert tight control on electrical signals in cells by regulating the inward/outward flow of the respective cation. As Na(+) and K(+) ions are both present in the body fluids, their respective ion channels should discriminate with high fidelity between the two competing metal ions, conducting the native cation while rejecting its monovalent contender (and other ions present in the cellular/extracellular milieu). Indeed, monovalent ion channels are characterized by remarkable metal selectivity. This striking ion selectivity of monovalent ion channels is astonishing in view of the close similarity between Na(+) and K(+): both are spherical alkali cations with the same charge, analogous chemical and physical properties, and similar ionic radii. The monovalent ion channel selectivity filters (SFs), which dictate the selectivity of the channel, differ in oligomericity, composition, overall charge, pore size, and solvent accessibility. This diversity of SFs raises the following intriguing questions: (1) What factors govern the metal competition in these SFs? (2) Which of these factors are exploited in achieving K(+) or Na(+) selectivity in the different types of monovalent channel SFs? These questions are addressed herein by summarizing results from recent studies. The results show that over billions of years of evolution, the SFs of potassium and sodium ion channels have adapted to the specific physicochemical properties of the cognate ion, using various strategies to enable them to efficiently select the native ion among its contenders.