title: KCNE1 alters the voltage sensor movements necessary to open the KCNQ1 channel gate.
abstract: The delayed rectifier I(Ks) potassium channel, formed by coassembly of α- (KCNQ1) and β- (KCNE1) subunits, is essential for cardiac function. Although KCNE1 is necessary to reproduce the functional properties of the native I(Ks) channel, the mechanism(s) through which KCNE1 modulates KCNQ1 is unknown. Here we report measurements of voltage sensor movements in KCNQ1 and KCNQ1/KCNE1 channels using voltage clamp fluorometry. KCNQ1 channels exhibit indistinguishable voltage dependence of fluorescence and current signals, suggesting a one-to-one relationship between voltage sensor movement and channel opening. KCNE1 coexpression dramatically separates the voltage dependence of KCNQ1/KCNE1 current and fluorescence, suggesting an imposed requirement for movements of multiple voltage sensors before KCNQ1/KCNE1 channel opening. This work provides insight into the mechanism by which KCNE1 modulates the I(Ks) channel and presents a mechanism for distinct β-subunit regulation of ion channel proteins.
authors.affiliation: Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Jeremiah D
authors.initials: JD
authors.lastname: Osteen
authors.forename: Carlos
authors.initials: C
authors.lastname: Gonzalez
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Sampson
authors.forename: Vivek
authors.initials: V
authors.lastname: Iyer
authors.forename: Santiago
authors.initials: S
authors.lastname: Rebolledo
authors.forename: H Peter
authors.initials: HP
authors.lastname: Larsson
authors.forename: Robert S
authors.initials: RS
authors.lastname: Kass
mesh_terms: D000465:Algorithms; D000818:Animals; D005260:Female; D005470:Fluorometry / Q000379:methods; D006801:Humans; D015640:Ion Channel Gating / Q000235:genetics / Q000502:physiology*; D051657:KCNQ1 Potassium Channel / Q000235:genetics / Q000502:physiology*; D008564:Membrane Potentials; D008845:Microinjections; D008954:Models, Biological; D009154:Mutation; D009865:Oocytes / Q000378:metabolism / Q000502:physiology; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000502:physiology*; D018075:RNA, Complementary / Q000008:administration & dosage / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D014982:Xenopus laevis
chemical_list: C489622:KCNE1 protein, human; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D024642:Potassium Channels, Voltage-Gated; D018075:RNA, Complementary