Regulation of KCNQ1/KCNE1 by β-catenin

beta-catenin, a multifunctional protein expressed in all tissues including the heart stimulates the expression of several genes important for cell proliferation. Signaling involving beta-catenin participates in directing cardiac development and in the pathophysiology of cardiac hypertrophy. Nothing is known, however, on the role of beta-catenin in the regulation of cardiac ion channels. The present study explored the functional interaction of beta-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 beta-catenin and the depolarization (up to + 80 mV) induced current (I-Ks) was determined using the two-electrode voltage clamp. As a result, beta-catenin enhanced IKs by 30%. The effect of beta-catenin on IKs was not affected by actinomycin D (10 mu M), an inhibitor of transcription, indicating that beta-catenin was not effective as transcription factor. Confocal microscopy revealed that beta-catenin enhanced the KCNE1/KCNQ1 protein abundance in the cell membrane. Exposure of the oocytes to brefeldin A (5 mM), an inhibitor of vesicle insertion, was followed by a decline of IKs, which was then similar in oocytes expressing KCNE1/KCNQ1 together with beta-catenin and in oocytes expressing KCNE1/KCNQ1 alone. In conclusion, beta-catenin enhances IKs by increasing the KCNE1/KCNQ1 protein abundance in the cell membrane, an effect requiring vesicle insertion into the cell membrane.