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Adipocytes modulate the electrophysiology of atrial myocytes: implications in obesity-induced atrial fibrillation

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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 (APD90). 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 APD90 (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.

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Acknowledgments

The current study was supported by Grants (NSC99-2314-B-016-034-MY3, NSC99-2628-B-038-011-MY3, NSC100-2628-B-038-001-MY4, NSC100-2325-B-010-005, and NSC100-2314-B-038-027-MY3) from the National Science Council of Taiwan, from the Center of Excellence for Clinical Trial and Research in Neuroscience (DOH101-TD-B-111-003), (100-wf-eva-01, 100-wf-eva-12, 100-swf-01, 100-swf-06, 101-wf-eva-11 and 101-wf-phd-01) from Taipei Medical University-Wan Fang Hospital, and (V100C-109, V101C-060) from Taipei Veterans General Hospital.

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None to be declared.

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Authors and Affiliations

  1. Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, 111 Hsin-Lung Road, Sec. 3, Taipei, Taiwan

    Yung-Kuo Lin & Yi-Jen Chen

  2. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Yung-Kuo Lin, Jenn-Han Chen & Yi-Jen Chen

  3. Department of Biomedical Engineering and Institute of Physiology, National Defense Medical Center, Taipei, Taiwan

    Yao-Chang Chen

  4. Research Laboratory, Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

    Jenn-Han Chen

  5. School of Medicine, National Yang-Ming University, Taipei, Taiwan

    Shih-Ann Chen

  6. Division of Cardiology and Cardiovascular Research Center, Veterans General Hospital, Taipei, Taipei, Taiwan

    Shih-Ann Chen

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Correspondence to Yi-Jen Chen.

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Lin, YK., Chen, YC., Chen, JH. et al. Adipocytes modulate the electrophysiology of atrial myocytes: implications in obesity-induced atrial fibrillation. Basic Res Cardiol 107, 293 (2012). https://doi.org/10.1007/s00395-012-0293-1

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