title: Remodeling of atrial ATP-sensitive K⁺ channels in a model of salt-induced elevated blood pressure.
abstract: Hypertension is associated with the development of atrial fibrillation; however, the electrophysiological consequences of this condition remain poorly understood. ATP-sensitive K(+) (K(ATP)) channels, which contribute to ventricular arrhythmias, are also expressed in the atria. We hypothesized that salt-induced elevated blood pressure (BP) leads to atrial K(ATP) 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 (APD(90)). Excised patch clamping was performed to quantify K(ATP) channel properties and density. K(ATP) channel protein expression was also evaluated. Atrial arrhythmia inducibility was 22% higher in HS hearts compared with control hearts. ERP and APD(90) 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 APD(90) in HS hearts compared with untreated HS hearts. K(ATP) 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, K(ATP) 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.
authors: Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, New York 10016, USA.
authors: Joshua M
authors: JM
authors: Lader
authors: Carolina
authors: C
authors: Vasquez
authors: Li
authors: L
authors: Bao
authors: Karen
authors: K
authors: Maass
authors: Jiaxiang
authors: J
authors: Qu
authors: Eirini
authors: E
authors: Kefalogianni
authors: Glenn I
authors: GI
authors: Fishman
authors: William A
authors: WA
authors: Coetzee
authors: Gregory E
authors: GE
authors: Morley
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000200:Action Potentials; D000704:Analysis of Variance; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001281:Atrial Fibrillation / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D016275:Atrial Function / Q000187:drug effects; D001794:Blood Pressure; D004195:Disease Models, Animal; D004562:Electrocardiography; D005355:Fibrosis; D006325:Heart Atria / Q000378:metabolism / Q000503:physiopathology; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D011955:Receptors, Drug / Q000378:metabolism; D012032:Refractory Period, Electrophysiological; D012508:Sarcolemma / Q000378:metabolism; D017673:Sodium Chloride, Dietary; D064233:Sulfonylurea Receptors; D013997:Time Factors; D056969:Voltage-Sensitive Dye Imaging
chemical_list: D018528:ATP-Binding Cassette Transporters; D000889:Anti-Arrhythmia Agents; D054086:KATP Channels; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D017673:Sodium Chloride, Dietary; D064233:Sulfonylurea Receptors; D011188:Potassium