Mol Membr Biol 2012 Jan 01;293-4:87-94. doi: 10.3109/09687688.2012.678017.

Regulation of KCNQ1/KCNE1 by β-catenin.

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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.

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Species referenced: Xenopus
Genes referenced: ctnnb1 kcne1 kcnq1