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

Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8792-7. doi: 10.1073/pnas.141233398. Epub 2001 Jul 3.


The voltage-dependent K(+) channel responsible for the slowly activating delayed 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, such 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 associated with fecal Na(+) and K(+) wasting and have lower plasma K(+) concentration and higher levels of aldosterone than wild-type mice. Although plasma aldosterone can be suppressed by low K(+) diets or stimulated by low Na(+) diets, a high 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) despite lower plasma K(+) in kcne1(-/-) mice. This exacerbated aldosterone production in kcne1(-/-) mice is accompanied by an abnormally high plasma renin concentration, which could partly explain the hyperaldosteronism. In addition, we found that KCNE1 and KCNQ1 mRNAs are expressed in the zona glomerulosa of adrenal glands where I(Ks) may directly participate in the control of aldosterone production by plasma K(+). These results, which show that KCNE1 and I(Ks) are involved in K(+) homeostasis, might have important implications for patients with I(Ks)-related long QT syndrome, because hypokalemia is a well known risk factor for the occurrence of torsades de pointes ventricular arrhythmia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldosterone / blood
  • Aldosterone / metabolism*
  • Animals
  • Blood Pressure
  • Colon / metabolism
  • Disease Models, Animal
  • Electrocardiography
  • Feces
  • Gene Expression
  • Humans
  • Ions / metabolism
  • KCNQ Potassium Channels
  • KCNQ1 Potassium Channel
  • Long QT Syndrome / congenital*
  • Long QT Syndrome / metabolism
  • Mice
  • Mice, Knockout
  • Potassium / blood
  • Potassium / metabolism*
  • Potassium Channels / genetics
  • Potassium Channels / physiology*
  • Potassium Channels, Voltage-Gated*
  • Renin / blood
  • Sodium / metabolism
  • Sodium / urine
  • Tissue Distribution


  • Ions
  • KCNQ Potassium Channels
  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human
  • Kcnq1 protein, mouse
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • potassium channel protein I(sk)
  • Aldosterone
  • Sodium
  • Renin
  • Potassium