title: The ligand-sensitive gate of a potassium channel lies close to the selectivity filter.
abstract: Potassium channels selectively conduct K(+) ions across cell membranes and have key roles in cell excitability. Their opening and closing can be spontaneous or controlled by membrane voltage or ligand binding. We used Ba(2+) as a probe to determine the location of the ligand-sensitive gate in an inwardly rectifying K(+) channel (Kir6.2). To a K(+) channel, Ba(2+) and K(+) are of similar sizes, but Ba(2+) blocks the pore by binding within the selectivity filter. We found that internal Ba(2+) could still access its binding site when the channel was shut, which indicates that the ligand-sensitive gate lies above the Ba(2+)-block site, and thus within or above the selectivity filter. This is in marked contrast to the voltage-dependent gate of K(V) channels, which is located at the intracellular mouth of the pore.
authors.affiliation: University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Proks
authors.forename: Jennifer F
authors.initials: JF
authors.lastname: Antcliff
authors.forename: Frances M
authors.initials: FM
authors.lastname: Ashcroft
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D019943:Amino Acid Substitution; D000818:Animals; D001464:Barium / Q000378:metabolism; D001665:Binding Sites; D002104:Cadmium / Q000378:metabolism; D002413:Cations, Divalent / Q000378:metabolism; D005260:Female; D015640:Ion Channel Gating / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects; D008024:Ligands; D051379:Mice; D008954:Models, Biological; D008970:Molecular Weight; D020125:Mutation, Missense; D009865:Oocytes; D017354:Point Mutation; D011188:Potassium / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D012834:Silver / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D002413:Cations, Divalent; D008024:Ligands; D024661:Potassium Channels, Inwardly Rectifying; D011994:Recombinant Proteins; D002104:Cadmium; D001464:Barium; D012834:Silver; D000255:Adenosine Triphosphate; D011188:Potassium