Functional coupling of human beta(3)-adrenoreceptors to the KvLQT1/MinK potassium channel

The slow component of the delayed rectifier potassium current (IKs) plays a n important role during repolarization in the human heart. Life-threatening arrhythmias can be triggered by sympathetic stimulation, presumably acting on IKs. The ion channel responsible for the IKs current is made of two pro teins, the KvLQT1 protein and the MinK protein, In this study, we investiga ted the effects of adrenergic stimulation on the KvLQT1/MinK channel by coe xpressing KvLQT1/MinK channels with the human beta(3)-adrenoreceptor subuni t heterologously in Xenopus oocytes, Western blot experiments revealed that beta(3)-adrenoreceptor proteins appear in the cell membrane of Xenopus ooc ytes, when the corresponding cRNA was injected. In electrophysiological mea surements we found that stimulation with the beta-adrenergic agonist isopro terenol increased the current amplitude of the beta(3)/KvLQT1/MinK complex up to 237% with an ED50 of 8 nM, a value similar to that found on IKs in gu inea pig cardiomyocytes. When oocytes with beta(3)/KvLQT1/MinK were preincu bated with cholera toxin (2 mu g/ml), an activator of G(S) proteins, the ba sal current amplitude of the beta(3)/KvLQT1/MinK complex was increased 3.1- fold, and the current amplitude increase by isoproterenol was drastically r educed, indicating that the signal transduction cascade was mediated via G( s) proteins. The knowledge about functional coupling of the human beta(3)-a drenoreceptor to KvLQT1/MinK channels reveals interesting aspects about the genesis and therapy of arrhythmias.