title: Adipocytes modulate the electrophysiology of atrial myocytes: implications in obesity-induced atrial fibrillation.
abstract: Obesity is an important risk factor for atrial fibrillation (AF). Increased epicardial adipose tissue in obesity can enhance inflammation and plays an important role in the pathophysiology of AF. However, it is not clear whether epicardial adipocytes directly modulate the electrophysiological characteristics of atrial myocytes. Whole-cell patch clamp was used to record the action potentials (APs) and ionic currents in isolated rabbit left atrium (LA) myocytes incubated with and without (control) isolated adipocytes from epicardial, retrosternal, or abdominal adipose tissues, or adipocytes-conditioned supernatant for 2-4 h. Compared to control LA myocytes (n = 22), LA myocytes incubated with epicardial (n = 17), retrosternal (n = 18), or abdominal adipocytes (n = 22) had longer (80 ± 3, 109 ± 6, 109 ± 6, and 110 ± 7 ms, p < 0.001) 90 % AP durations (APD(90)). LA myocytes incubated with epicardial adipocytes had a more-positive resting membrane potential (RMP) than control LA myocytes (-57 ± 1 mV vs. -63.4 ± 1.4 mV, p < 0.05). However, LA myocytes (n = 32) incubated with supernatant had longer APD(90) (93 ± 3 ms, p < 0.05), but similar RMP values (-62 ± 2 mV, p > 0.05) in comparison to control myocytes. Epicardial adipocyte-incubated LA myocytes had larger late sodium currents, L-type calcium currents, and transient outward potassium currents, but smaller delayed rectifier potassium and inward rectifier potassium currents than control LA myocytes. Moreover, isoproterenol (10 nM) induced a higher incidence (67 vs. 22 %, p < 0.05) of triggered beats in adipocytes-incubated LA myocytes (n = 12) than in control LA myocytes (n = 9). In conclusion, adipocytes can directly modulate the electrophysiological properties and ion currents, causing higher arrhythmogenesis in LA myocytes.
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, 111 Hsin-Lung Road Sec. 3, Taipei, Taiwan.
authors.forename: Yung-Kuo
authors.initials: YK
authors.lastname: Lin
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chen
authors.forename: Jenn-Han
authors.initials: JH
authors.lastname: Chen
authors.forename: Shih-Ann
authors.initials: SA
authors.lastname: Chen
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Chen
mesh_terms: D000200:Action Potentials; D017667:Adipocytes / Q000502:physiology*; D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology*; D006325:Heart Atria / Q000166:cytology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D032383:Myocytes, Cardiac / Q000502:physiology*; D009765:Obesity / Q000150:complications*; D011817:Rabbits
chemical_list: D007545:Isoproterenol