Remodeling of atrial ATP-sensitive K+ channels in a model of salt-induced elevated blood pressure

Joshua M. Lader, Carolina Vasquez, Li Bao, Karen Maass, Jiaxiang Qu, Eirini Kefalogianni, Glenn I. Fishman, William A. Coetzee, Gregory E. Morley

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Hypertension is associated with the development of atrial fibrillation; however, the electrophysiological consequences of this condition remain poorly understood. ATP-sensitive K+ (KATP) channels, which contribute to ventricular arrhythmias, are also expressed in the atria. We hypothesized that salt-induced elevated blood pressure (BP) leads to atrial KATP channel activation and increased arrhythmia inducibility. Elevated BP was induced in mice with a high-salt diet (HS) for 4 wk. High-resolution optical mapping was used to measure atrial arrhythmia inducibility, effective refractory period (ERP), and action potential duration at 90% repolarization (APD90). Excised patch clamping was performed to quantify KATP channel properties and density. KATP channel protein expression was also evaluated. Atrial arrhythmia inducibility was 22% higher in HS hearts compared with control hearts. ERP and APD90 were significantly shorter in the right atrial appendage and left atrial appendage of HS hearts compared with control hearts. Perfusion with 1 μM glibenclamide or 300 μM tolbutamide significantly decreased arrhythmia inducibility and prolonged APD90 in HS hearts compared with untreated HS hearts. KATP channel density was 156% higher in myocytes isolated from HS animals compared with control animals. Sulfonylurea receptor 1 protein expression was increased in the left atrial appendage and right atrial appendage of HS animals (415% and 372% of NS animals, respectively). In conclusion, KATP channel activation provides a mechanistic link between salt-induced elevated BP and increased atrial arrhythmia inducibility. The findings of this study have important implications for the treatment and prevention of atrial arrhythmias in the setting of hypertensive heart disease and may lead to new therapeutic approaches.

Original languageEnglish
Pages (from-to)H964-H974
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume301
Issue number3
DOIs
StatePublished - Sep 2011

Keywords

  • Action potentials
  • Arrhythmia mechanisms
  • Cardiac remodeling
  • Potassium channel
  • Salt sensitivity hypertension

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