Document Detail


Remodeling of atrial ATP-sensitive K⁺ channels in a model of salt-induced elevated blood pressure.
MedLine Citation:
PMID:  21724863     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Joshua M Lader; Carolina Vasquez; Li Bao; Karen Maass; Jiaxiang Qu; Eirini Kefalogianni; Glenn I Fishman; William A Coetzee; Gregory E Morley
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-07-01
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  301     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-08-31     Completed Date:  2011-11-01     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H964-74     Citation Subset:  IM    
Affiliation:
Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, New York 10016, USA.
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MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters / metabolism
Action Potentials
Analysis of Variance
Animals
Anti-Arrhythmia Agents / pharmacology
Atrial Fibrillation / etiology,  metabolism*,  pathology,  physiopathology,  prevention & control
Atrial Function* / drug effects
Blood Pressure*
Disease Models, Animal
Electrocardiography
Fibrosis
Heart Atria / metabolism,  physiopathology
Hypertension / drug therapy,  etiology,  metabolism*,  pathology,  physiopathology
KATP Channels / antagonists & inhibitors,  metabolism*
Male
Mice
Myocytes, Cardiac / drug effects,  metabolism*,  pathology
Patch-Clamp Techniques
Potassium / metabolism*
Potassium Channel Blockers / pharmacology
Potassium Channels, Inwardly Rectifying / metabolism
Receptors, Drug / metabolism
Refractory Period, Electrophysiological
Sarcolemma / metabolism
Sodium Chloride, Dietary*
Time Factors
Voltage-Sensitive Dye Imaging
Grant Support
ID/Acronym/Agency:
1-S10-RR-026681/RR/NCRR NIH HHS; 1-T32-HL-098129/HL/NHLBI NIH HHS; HL-076751/HL/NHLBI NIH HHS; HL-081336/HL/NHLBI NIH HHS; HL-085820/HL/NHLBI NIH HHS; HL-093563/HL/NHLBI NIH HHS; HL-105046/HL/NHLBI NIH HHS; HL-82727/HL/NHLBI NIH HHS; R01 HL081336/HL/NHLBI NIH HHS; R01 HL082727/HL/NHLBI NIH HHS; S10 RR026881/RR/NCRR NIH HHS; T32 HL098129/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 0/KATP Channels; 0/Potassium Channel Blockers; 0/Potassium Channels, Inwardly Rectifying; 0/Receptors, Drug; 0/Sodium Chloride, Dietary; 0/sulfonylurea receptor; 7440-09-7/Potassium
Comments/Corrections

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