Tumor necrosis factor-α alters calcium handling and increases arrhythmogenesis of pulmonary vein cardiomyocytes

Shih Huang Lee, Yao Chang Chen, Yi Jen Chen, Shih Lin Chang, Ching Tai Tai, Wanwarang Wongcharoen, Hung I. Yeh, Cheng I. Lin, Shih Ann Chen

研究成果: 雜誌貢獻文章同行評審

110 引文 斯高帕斯(Scopus)


Inflammation and abnormal calcium homeostasis play important roles in atrial fibrillation. Tumor necrosis factor-α (TNFα), a proinflammatory cytokine, can induce cardiac arrhythmias. Pulmonary veins (PVs) are critical in initiating paroxysmal atrial fibrillation. This study was designed to investigate whether TNFα may change the calcium handling and arrhythmogenic activity of PV cardiomyocytes. We used whole-cell patch clamp and indo-1 fluorimetric ratio technique to investigate the action potentials, ionic currents and intracellular calcium in isolated rabbit single PV cardiomyocytes with and without (control) incubation with TNFα (25 ng/ml) for 7-10 h. The expression of sarcoplasmic reticulum ATPase in the control and TNFα-treated PV cardiomyocytes was evaluated by confocal micrographs and Western blot. We found that the spontaneous beating rates were similar between the control (n = 45) and TNFα-treated (n = 28) PV cardiomyocytes. Compared with the control PV cardiomyocytes, the TNFα-treated PV cardiomyocytes had significantly a larger amplitude of the delayed afterdepolarizations (6.0 ± 1.7 vs. 2.6 ± 0.8 mV, P < 0.05), smaller L-type calcium currents, larger transient inward currents, larger Na+-Ca2+ exchanger currents, a smaller intracellular calcium transient, smaller sarcoplasmic reticulum calcium content, larger diastolic intracellular calcium, a longer decay portion of the calcium transient (Tau), and a decreased sarcoplasmic reticulum ATPase expression. In conclusion, TNFα can increase the PV arrhythmogenicity and induce an abnormal calcium homeostasis, thereby causing inflammation-related atrial fibrillation.

頁(從 - 到)1806-1815
期刊Life Sciences
出版狀態已發佈 - 4月 17 2007

ASJC Scopus subject areas

  • 生物化學、遺傳與分子生物學 (全部)
  • 藥理學、毒理學和藥劑學 (全部)


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