title: High-fat diet-dependent modulation of the delayed rectifier K(+) current in adult guinea pig atrial myocytes.
abstract: Obesity is associated with hyperlipidemia, electrical remodeling of the heart, and increased risk of supraventricular arrhythmias in both male and female patients. The delayed rectifier K(+) current (IK), is an important regulator of atrial repolarization. There is a paucity of studies on the functional role of IK in response to obesity. Here, we assessed the obesity-mediated functional modulation of IK in low-fat diet (LFD), and high-fat diet (HFD) fed adult guinea pigs. Guinea pigs were randomly divided into control and obese groups fed, ad libitum, with a LFD (10 kcal% fat) or a HFD (45 kcal% fat) respectively. Action potential duration (APD), and IK were studied in atrial myocytes and IKr and IKs in HEK293 cells using whole-cell patch clamp electrophysiology. HFD guinea pigs displayed a significant increase in body weight, total cholesterol and total triglycerides within 50 days. Atrial APD at 30% (APD30) and 90% (APD90) repolarization were shorter, while atrial IK density was significantly increased in HFD guinea pigs. Exposure to palmitic acid (PA) increased heterologously expressed IKr and IKs densities, while oleic acid (OA), severely reduced IKr and had no effect on IKs. The data are first to show that in obese guinea pigs abbreviated APD is due to increased IK density likely through elevations of PA. Our findings may have crucial implications for targeted treatment options for obesity-related arrhythmias.
authors.affiliation: Department of Physiology & Cellular Biophysics, Columbia University, New York, NY, United States.
authors.forename: Ademuyiwa S
authors.initials: AS
authors.lastname: Aromolaran
authors.affiliation: Department of Physiology & Cellular Biophysics, Columbia University, New York, NY, United States.
authors.forename: Henry M
authors.initials: HM
authors.lastname: Colecraft
authors.affiliation: Cardiovascular Research Program, VA New York Harbor Healthcare System, United States; Department of Medicine, State University of New York Downstate Medical Center, Brooklyn, New York, NY, United States; Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York, NY, United States; Department of Pharmacology, State University of New York Downstate Medical Center, Brooklyn, New York, NY, United States; Department of Medicine, New York University School of Medicine, New York, NY, United States. Electronic address: mohamed.boutjdir@va.gov.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Boutjdir
mesh_terms: D000200:Action Potentials; D000818:Animals; D059305:Diet, High-Fat / Q000379:methods*; D004041:Dietary Fats / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000503:physiopathology*; D006329:Heart Conduction System / Q000503:physiopathology; D008297:Male; D008564:Membrane Potentials; D032383:Myocytes, Cardiac; D009765:Obesity / Q000503:physiopathology*; D019308:Palmitic Acid / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*
chemical_list: D004041:Dietary Fats; D019308:Palmitic Acid; D011188:Potassium
keywords: Atrial myocytes; Guinea pig; High-fat diet; I(K); Obesity