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.

Keywords::

• IKs
• cardiac repolarization
• vesicle trafficking
• cardiac hypertrophy

Acknowledgements

This work was supported by the DFG (GRK 1302/1 and SFB 773) and the IZKF of the University of Tübingen (Nachwuchsgruppe). The authors gratefully acknowledge the meticulous preparation of the manuscript by Tanja Loch and Sari Rübe.

Declaration of interest : The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.