High-fat diet-dependent modulation of the delayed rectifier K+ current in adult guinea pig atrial myocytes

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 (I-K), is an important regulator of atrial repolarization. There is a paucity of studies on the functional role of I-K in response to obesity. Here, we assessed the obesity-mediated functional modulation of I-K 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 I-K were studied in atrial myocytes and I-Kr and I-Ks 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% (APD(30)) and 90% (APD(90)) repolarization were shorter, while atrial I-K density was significantly increased in HFD guinea pigs. Exposure to palmitic acid (PA) increased heterologously expressed I-Kr and I-Ks densities, while oleic acid (OA), severely reduced I-Kr and had no effect on I-Ks. The data are first to show that in obese guinea pigs abbreviated APD is due to increased I-K density likely through elevations of PA. Our findings may have crucial implications for targeted treatment options for obesity-related arrhythmias. Published by Elsevier Inc.