title: Alteration of ionic selectivity of a K+ channel by mutation of the H5 region.
abstract: The high ionic selectivity of K+ channels is a unifying feature of this diverse class of membrane proteins. Though K+ channels differ widely in regulation and kinetics, physiological studies have suggested a common structure: a single file pore containing multiple ion-binding sites and having broader vestibules at both ends. We have used site-directed mutagenesis and single-channel recordings to identify a molecular region that influences ionic selectivity in a cloned A-type K+ channel from Drosophila. Single amino-acid substitutions in H5, the fifth hydrophobic region, enhanced the passage of NH4+ and Rb+, ions with diameters larger than K+, without compromising the ability of the channel to exclude the smaller cation, Na+. The mutations that substantially altered selectivity had little effect on the gating properties of the channel. We conclude that the H5 region is likely to line the pore of the K+ channel.
authors.affiliation: Department of Molecular and Cellular Physiology, Stanford University Medical Center, California 94305-5426.
authors.forename: A J
authors.initials: AJ
authors.lastname: Yool
authors.forename: T L
authors.initials: TL
authors.lastname: Schwarz
mesh_terms: D000595:Amino Acid Sequence; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D004331:Drosophila melanogaster; D004553:Electric Conductivity / Q000187:drug effects; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics; D012413:Rubidium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013329:Structure-Activity Relationship; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014982:Xenopus laevis
chemical_list: D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D000641:Ammonia; D012964:Sodium; D012413:Rubidium; D011188:Potassium