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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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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DOI: https://doi.org/10.1007/s00395-012-0293-1