title: Domain-domain interactions determine the gating, permeation, pharmacology, and subunit modulation of the IKs ion channel.
abstract: Voltage-gated ion channels generate electrical currents that control muscle contraction, encode neuronal information, and trigger hormonal release. Tissue-specific expression of accessory (β) subunits causes these channels to generate currents with distinct properties. In the heart, KCNQ1 voltage-gated potassium channels coassemble with KCNE1 β-subunits to generate the IKs current (Barhanin et al., 1996; Sanguinetti et al., 1996), an important current for maintenance of stable heart rhythms. KCNE1 significantly modulates the gating, permeation, and pharmacology of KCNQ1 (Wrobel et al., 2012; Sun et al., 2012; Abbott, 2014). These changes are essential for the physiological role of IKs (Silva and Rudy, 2005); however, after 18 years of study, no coherent mechanism explaining how KCNE1 affects KCNQ1 has emerged. Here we provide evidence of such a mechanism, whereby, KCNE1 alters the state-dependent interactions that functionally couple the voltage-sensing domains (VSDs) to the pore.
authors.affiliation: Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Diseases, Washington University in St Louis, St Louis, United States.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Zaydman
authors.affiliation: Theory, Modeling, and Simulations, UMR 7565, Université de Lorraine, Nancy, France.
authors.forename: Marina A
authors.initials: MA
authors.lastname: Kasimova
authors.affiliation: Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Diseases, Washington University in St Louis, St Louis, United States.
authors.forename: Kelli
authors.initials: K
authors.lastname: McFarland
authors.affiliation: Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Diseases, Washington University in St Louis, St Louis, United States.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Beller
authors.affiliation: Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Diseases, Washington University in St Louis, St Louis, United States.
authors.forename: Panpan
authors.initials: P
authors.lastname: Hou
authors.affiliation: Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Diseases, Washington University in St Louis, St Louis, United States.
authors.forename: Holly E
authors.initials: HE
authors.lastname: Kinser
authors.affiliation: Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Diseases, Washington University in St Louis, St Louis, United States.
authors.forename: Hongwu
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Diseases, Washington University in St Louis, St Louis, United States.
authors.forename: Guohui
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Diseases, Washington University in St Louis, St Louis, United States.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Shi
authors.affiliation: Theory, Modeling, and Simulations, UMR 7565, Université de Lorraine, Nancy, France.
authors.forename: Mounir
authors.initials: M
authors.lastname: Tarek
authors.affiliation: Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Diseases, Washington University in St Louis, St Louis, United States.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Cui
mesh_terms: D000818:Animals; D005260:Female; D015640:Ion Channel Gating; D051657:KCNQ1 Potassium Channel / Q000378:metabolism; D008958:Models, Molecular; D010539:Permeability; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000378:metabolism*; D014981:Xenopus
chemical_list: D051657:KCNQ1 Potassium Channel; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits
keywords: KCNE; KCNQ; accessory subunit; biophysics; electromechanical coupling; ion channel; structural biology; voltage-dependent gating; xenopus