title: Regulation of KCNQ1/KCNE1 by β-catenin.
abstract: β-catenin, a multifunctional protein expressed in all tissues including the heart stimulates the expression of several genes important for cell proliferation. Signaling involving ß-catenin participates in directing cardiac development and in the pathophysiology of cardiac hypertrophy. Nothing is known, however, on the role of β-catenin in the regulation of cardiac ion channels. The present study explored the functional interaction of β-catenin and KCNE1/KCNQ1, the K⁺ channel complex underlying the slowly activating outwardly rectifying K⁺ current. To this end, KCNE1/KCNQ1 was expressed in Xenopus oocytes with and without β-catenin and the depolarization (up to + 80 mV) induced current (I(Ks)) was determined using the two-electrode voltage clamp. As a result, β-catenin enhanced I(Ks) by 30%. The effect of β-catenin on I(Ks) was not affected by actinomycin D (10 μM), an inhibitor of transcription, indicating that β-catenin was not effective as transcription factor. Confocal microscopy revealed that β-catenin enhanced the KCNE1/KCNQ1 protein abundance in the cell membrane. Exposure of the oocytes to brefeldin A (5 μM), an inhibitor of vesicle insertion, was followed by a decline of I(Ks), which was then similar in oocytes expressing KCNE1/KCNQ1 together with β-catenin and in oocytes expressing KCNE1/KCNQ1 alone. In conclusion, β-catenin enhances I(Ks) by increasing the KCNE1/KCNQ1 protein abundance in the cell membrane, an effect requiring vesicle insertion into the cell membrane.
authors.affiliation: Department of Physiology, University of Tübingen, Tübingen, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Wilmes
authors.forename: Roberta
authors.initials: R
authors.lastname: Haddad-Tóvolli
authors.forename: Ioana
authors.initials: I
authors.lastname: Alesutan
authors.forename: Carlos
authors.initials: C
authors.lastname: Munoz
authors.forename: Mentor
authors.initials: M
authors.lastname: Sopjani
authors.forename: Lisann
authors.initials: L
authors.lastname: Pelzl
authors.forename: Evgenii
authors.initials: E
authors.lastname: Bogatikov
authors.forename: Grazia
authors.initials: G
authors.lastname: Fedele
authors.forename: Caterina
authors.initials: C
authors.lastname: Faggio
authors.forename: Guiscard
authors.initials: G
authors.lastname: Seebohm
authors.forename: Michael
authors.initials: M
authors.lastname: Föller
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D014981:Xenopus; D029867:Xenopus Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D015820:Cadherins; C530745:KCNE1 protein, Xenopus; D051657:KCNQ1 Potassium Channel; D024642:Potassium Channels, Voltage-Gated; D029867:Xenopus Proteins; D051176:beta Catenin; D011188:Potassium