title: Influence of amino-terminal structures on kinetic transitions between several closed and open states in human erg K+ channels.
abstract: Gating kinetics of human ether-a-go-go (eag)-related gene (HERG) K+ channel expressed in Xenopus oocytes was studied using non-inactivating channel variants carrying different structural modifications in the amino terminus. A kinetics model was elaborated to describe the behavior of full-length channels, that includes at least three open states besides the three closed states previously proposed. Deletion of the HERG-specific proximal domain (HERG D138-373) accelerated all individual forward transitions between closed states. Whereas relatively large amplitude depolarizations were required to drive full-length HERG channels to more distal open states, these were reached more easily in channels without proximal domain. Alteration of the initial eag/PAS domain by introduction of a short amino-acid sequence at the beginning of the amino terminus did not alter transitions between closed states, but prevented the channels from reaching the farthest open states that determine slower deactivation rates. This indicates that the presence of specific amino-terminal structures can be correlated with the occurrence of distinctive molecular transitions. It also demonstrates that both proximal and eag/PAS domains in the amino terminus contribute to set the gating characteristics of HERG channels.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Oviedo, Edificio Santiago Gascón, Campus del Cristo, E-33006, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Gómez-Varela
authors.forename: P
authors.initials: P
authors.lastname: de la Peña
authors.forename: J
authors.initials: J
authors.lastname: García
authors.forename: T
authors.initials: T
authors.lastname: Giráldez
authors.forename: F
authors.initials: F
authors.lastname: Barros
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D027682:Cation Transport Proteins; D003198:Computer Simulation; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D000939:Epitopes; D051638:Ether-A-Go-Go Potassium Channels; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D015640:Ion Channel Gating / Q000235:genetics*; D008564:Membrane Potentials / Q000235:genetics*; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000737:chemistry* / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D019655:Quantitative Trait, Heritable; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D046249:Transfer RNA Aminoacylation; D014981:Xenopus / Q000235:genetics / Q000378:metabolism
chemical_list: D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D000072237:ERG1 Potassium Channel; D000939:Epitopes; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG