Altered potassium balance and aldosterone secretion in a mouse model of human congenital long QT syndrome

The voltage-dependent K+ channel responsible for the slowly activating dela yed K+ current I-Ks is composed of pore-forming KCNQ1 and regulatory KCNE1 subunits, which are mutated in familial forms of cardiac long QT syndrome. Because KCNQ1 and KCNE1 genes also are expressed in epithelial tissues, suc h as the kidneys and the intestine, we have investigated the adaptation of KCNE1-deficient mice to different K+ and Na+ intakes, On a normal K+ diet, homozygous kcne1(-/-) mice exhibit signs of chronic volume depletion associ ated with fecal Na+ and K+ wasting and have lower plasma K+ concentration a nd higher levels of aldosterone than wild-type mice, Although plasma aldost erone can be suppressed by low K+ diets or stimulated by low Na+ diets, a h igh K+ diet provokes a tremendous increase of plasma aldosterone levels in kcne1(-/-) mice as compared with wild-type mice (7.1-fold vs. 1.8-fold) des pite lower plasma K+ in kcne1(-/-) mice. This exacerbated aldosterone produ ction in kcne1(-/-) mice is accompanied by an abnormally high plasma renin concentration, which could partly explain the hyperaldosteronism. In additi on, we found that KCNE1 and KCNQ1 mRNAs are expressed in the zona glomerulo sa of adrenal glands where I-Ks may directly participate in the control of aldosterone production by plasma K+, These results, which show that KCNE1 a nd I-Ks are involved in K+ homeostasis, might have important implications f or patients with I-Ks-related long QT syndrome, because hypokalemia is a we ll known risk factor for the occurrence of torsades de pointes ventricular arrhythmia.