Activation of voltage gated K⁺ channel Kv1.5 by β-catenin

Voltage-gated Kv1.5 channels are expressed in a wide variety of tissues including cardiac myocytes, smooth muscle and tumor cells. Kv1.5 channel activity is modified by N-cadherin, which in turn binds the multifunctional oncogenic protein β-catenin. The present experiments explored the effect of β-catenin on Kv1.5 channel activity. To this end, Kv1.5 was expressed in Xenopus oocytes with or without β-catenin and the voltage-gated Kv current determined by dual electrode voltage clamp. As a result, expression of β-catenin significantly increased the voltage-gated Kv current at positive potentials. The stimulating effect of β-catenin on Kv1.5 was not dependent on the stimulation of transcription since it was observed even in the presence of the transcription inhibitor actinomycin D. Specific antibody binding to surface Kv1.5 in Xenopus oocytes revealed that β-catenin enhances the membrane abundance of Kv1.5. Further experiments with brefeldin A showed that β-catenin fosters the insertion of Kv1.5 into rather than delaying the retrieval from the plasma membrane. According to electrophysiological recordings with mutant β-catenin, the effect on Kv1.5 requires the same protein domains that are required for association of β-catenin with cadherin. The experiments disclose a completely novel function of β-catenin, i.e. the regulation of Kv1.5 channel activity.