Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, 111 Hsin-Lung Road Sec. 3, Taipei, Taiwan.
Basic Res Cardiol. 2012 Sep;107(5):293. doi: 10.1007/s00395-012-0293-1. Epub 2012 Aug 12.
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.
肥胖是心房颤动（AF）的一个重要危险因素。肥胖症中的心外膜脂肪组织增加会增强炎症反应，并在 AF 的病理生理学中发挥重要作用。然而，尚不清楚心外膜脂肪细胞是否直接调节心房肌细胞的电生理特性。使用全细胞膜片钳记录在含有（实验组）和不含有（对照组）心外膜、胸骨后或腹部脂肪组织分离的脂肪细胞或脂肪细胞条件培养基孵育 2-4 小时的分离的兔左心房（LA）肌细胞的动作电位（APs）和离子电流。与对照组 LA 肌细胞（n=22）相比，实验组 LA 肌细胞（n=17）与心外膜脂肪细胞、胸骨后脂肪细胞或腹部脂肪细胞孵育后具有更长的（80±3、109±6、109±6 和 110±7 ms，p<0.001）90%AP 持续时间（APD90）。与对照组 LA 肌细胞相比，实验组 LA 肌细胞与心外膜脂肪细胞孵育后具有更正向的静息膜电位（RMP）（-57±1 mV 比-63.4±1.4 mV，p<0.05）。然而，与对照组肌细胞相比，实验组（n=32）与上清液孵育后具有更长的 APD90（93±3 ms，p<0.05），但 RMP 值相似（-62±2 mV，p>0.05）。与对照组 LA 肌细胞相比，实验组 LA 肌细胞与心外膜脂肪细胞孵育后具有更大的晚期钠电流、L 型钙电流和瞬间外向钾电流，但具有更小的延迟整流钾电流和内向整流钾电流。此外，异丙肾上腺素（10 nM）在心外膜脂肪细胞孵育的 LA 肌细胞（n=12）中引起更高的触发搏动发生率（67%比 22%，p<0.05），而在对照组 LA 肌细胞（n=9）中引起更高的触发搏动发生率（67%比 22%，p<0.05）。总之，脂肪细胞可以直接调节电生理特性和离子电流，导致 LA 肌细胞发生更高的心律失常。
