title: Molecular driving forces determining potassium channel slow inactivation.
abstract: K+ channels undergo a time-dependent slow inactivation process that plays a key role in modulating cellular excitability. Here we show that in the prokaryotic proton-gated K+ channel KcsA, the number and strength of hydrogen bonds between residues in the selectivity filter and its adjacent pore helix determine the rate and extent of C-type inactivation. Upon channel activation, the interaction between residues at positions Glu71 and Asp80 promotes filter constriction parallel to the permeation pathway, which affects K+-binding sites and presumably abrogates ion conduction. Coupling between these two positions results in a quantitative correlation between their interaction strength and the stability of the inactivated state. Engineering of these interactions in the eukaryotic voltage-dependent K+ channel Kv1.2 suggests that a similar mechanistic principle applies to other K+ channels. These observations provide a plausible physical framework for understanding C-type inactivation in K+ channels.
authors.affiliation: Department of Molecular Physiology and Biological Physics, University of Virginia, 1300 JPA, Charlottesville, Virginia 22908, USA.
authors.forename: Julio F
authors.initials: JF
authors.lastname: Cordero-Morales
authors.forename: Vishwanath
authors.initials: V
authors.lastname: Jogini
authors.forename: Anthony
authors.initials: A
authors.lastname: Lewis
authors.forename: Valeria
authors.initials: V
authors.lastname: Vásquez
authors.forename: D Marien
authors.initials: DM
authors.lastname: Cortes
authors.forename: Benoît
authors.initials: B
authors.lastname: Roux
authors.forename: Eduardo
authors.initials: E
authors.lastname: Perozo
mesh_terms: D000818:Animals; D001216:Asparagine / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006639:Histidine / Q000378:metabolism; D006860:Hydrogen Bonding; D015640:Ion Channel Gating / Q000502:physiology*; D051663:Kv1.2 Potassium Channel / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009865:Oocytes / Q000166:cytology / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D051381:Rats; D014982:Xenopus laevis
chemical_list: D001426:Bacterial Proteins; D051663:Kv1.2 Potassium Channel; D008081:Liposomes; D015221:Potassium Channels; C107790:prokaryotic potassium channel; D006639:Histidine; D001216:Asparagine