title: Aldosterone down-regulates the slowly activated delayed rectifier potassium current in adult guinea pig cardiomyocytes.
abstract: OBJECTIVE
  There is emerging evidence that the mineralocorticoid hormone aldosterone is associated with arrhythmias in cardiovascular disease. However, the effect of aldosterone on the slowly activated delayed rectifier potassium current (IK s ) remains poorly understood. The present study was designed to investigate the modulation of IK s by aldosterone.
  
  
  METHODS
  Adult guinea pigs were treated with aldosterone for 28 days via osmotic pumps. Standard glass microelectrode recordings and whole-cell patch-clamp techniques were used to record action potentials in papillary muscles and IK s in ventricular cardiomyocytes.
  
  
  RESULTS
  The aldosterone-treated animals exhibited a prolongation of the QT interval and action potential duration with a higher incidence of early afterdepolarizations. Patch-clamp recordings showed a significant down-regulation of IK s density in the ventricular myocytes of these treated animals. These aldosterone-induced electrophysiological changes were fully prevented by a combined treatment with spironolactone, a mineralocorticoid receptor (MR) antagonist. In addition, in in vitro cultured ventricular cardiomyocytes, treatment with aldosterone (sustained exposure for 24 h) decreased the IK s density in a concentration-dependent manner. Furthermore, a significant corresponding reduction in the mRNA/protein expression of IKs channel pore and auxiliary subunits, KCNQ1 and KCNE1 was detected in ventricular tissue from the aldosterone-treated animals.
  
  
  CONCLUSIONS
  Aldosterone down-regulates IK s by inhibiting the expression of KCNQ1 and KCNE1, thus delaying the ventricular repolarization. These results provide new insights into the mechanism underlying K(+) channel remodelling in heart disease and may explain the highly beneficial effects of MR antagonists in HF.
authors: Department of Pharmacology, Hebei Medical University, The Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, Hebei, China.|Heart Center, Hebei General Hospital, Shijiazhuang, China.
authors: Yankun
authors: Y
authors: Lv
authors: Department of Pharmacology, Hebei Medical University, The Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, Hebei, China.
authors: Song
authors: S
authors: Bai
authors: Department of Pharmacology, Hebei Medical University, The Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, Hebei, China.
authors: Hua
authors: H
authors: Zhang
authors: Department of Pharmacology, Hebei Medical University, The Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, Hebei, China.
authors: Hongxue
authors: H
authors: Zhang
authors: Department of Pharmacology, Hebei Medical University, The Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, Hebei, China.
authors: Jing
authors: J
authors: Meng
authors: Heart Center, Hebei General Hospital, Shijiazhuang, China.
authors: Li
authors: L
authors: Li
authors: Department of Pharmacology, Hebei Medical University, The Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, Hebei, China.
authors: Yanfang
authors: Y
authors: Xu
mesh_terms: D000450:Aldosterone / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D051668:Delayed Rectifier Potassium Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D006168:Guinea Pigs; D007279:Injections, Subcutaneous; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D051668:Delayed Rectifier Potassium Channels; D026902:Potassium Channel Blockers; D000450:Aldosterone