Kellenberger S Gautschi I Schild L 1999 The epithelial Na+ channel (ENaC) belongs to a new class of channel proteins called the ENaC/DEG superfamily involved in epithelial Na+ transport, mechanotransduction, and neurotransmission. The role of ENaC in Na+ homeostasis and in the control of blood pressure has been demonstrated recently by the identification of mutations in ENaC beta and gamma subunits causing hypertension. The function of ENaC in Na+ reabsorption depends critically on its ability to discriminate between Na+ and other ions like K+ or Ca2+. ENaC is virtually impermeant to K+ ions, and the molecular basis for its high ionic selectivity is largely unknown. We have identified a conserved Ser residue in the second transmembrane domain of the ENaC alpha subunit (alphaS589), which when mutated allows larger ions such as K+, Rb+, Cs+, and divalent cations to pass through the channel. The relative ion permeability of each of the alphaS589 mutants is related inversely to the ionic radius of the permeant ion, indicating that alphaS589 mutations increase the molecular cutoff of the channel by modifying the pore geometry at the selectivity filter. Proper geometry of the pore is required to tightly accommodate Na+ and Li+ ions and to exclude larger cations. We provide evidence that ENaC discriminates between cations mainly on the basis of their size and the energy of dehydration. application/pdf https://sonar.ch/global/documents/139074 eng info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.96.7.4170 info:eu-repo/semantics/altIdentifier/pmid/10097182 info:eu-repo/semantics/openAccess Proceedings of the National Academy of Sciences of the United States of America. - 1999 Amino Acid Sequence Animals Cations, Divalent Cations, Monovalent Conserved Sequence Epithelial Sodium Channels Female Macromolecular Substances Membrane Potentials Models, Molecular Molecular Sequence Data Mutagenesis, Site-Directed Oocytes Point Mutation Protein Conformation Rats Recombinant Proteins Sequence Alignment Sequence Homology, Amino Acid Serine Sodium Channels Xenopus laevis A single point mutation in the pore region of the epithelial Na+ channel changes ion selectivity by modifying molecular sieving. http://purl.org/coar/resource_type/c_6501