Hwang Hwong-Ru, Tai Buh-Yuan, Cheng Pao-Yun, Chen Ping-Nan, Sung Ping-Jyun, Wen Zhi-Hong, Hsu Chih-Hsueng
Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 804, Taiwan.
Division of Cardiology, Department of Medicine, E-Da Hospital, Kaohsiung 824, Taiwan.
Mar Drugs. 2017 Jan 24;15(2):25. doi: 10.3390/md15020025.
Severe bacterial infections caused by sepsis always result in profound physiological changes, including fever, hypotension, arrhythmia, necrosis of tissue, systemic multi-organ dysfunction, and finally death. The lipopolysaccharide (LPS) provokes an inflammatory response under sepsis, which may increase propensity to arrhythmogenesis. Excavatolide B (EXCB) possesses potent anti-inflammatory effects. However, it is not clear whether EXCB could modulate the electrophysiological characteristics and calcium homeostasis of atrial myocytes. This study investigated the effects of EXCB on the atrial myocytes exposed to lipopolysaccharide. A whole-cell patch clamp and indo-1 fluorimetric ratio technique was employed to record the action potential (AP), ionic currents, and intracellular calcium ([Ca]) in single, isolated rabbit left atrial (LA) cardiomyocytes, with and without LPS (1 μg/mL) and LPS + EXCB administration (10 μM) for 6 ± 1 h, in order to investigate the role of EXCB on atrial electrophysiology. In the presence of LPS, EXCB-treated LA myocytes ( = 13) had a longer AP duration at 20% (29 ± 2 vs. 20 ± 2 ms, < 0.05), 50% (52 ± 4 vs. 40 ± 3 ms, < 0.05), and 90% (85 ± 5 vs. 68 ± 3 ms, < 0.05), compared to the LPS-treated cells ( = 12). LPS-treated LA myocytes showed a higher late sodium current, Na⁺/Ca exchanger current, transient outward current, and delayed rectifier potassium current, but a lower l-type Ca current, than the control LA myocytes. Treatment with EXCB reversed the LPS-induced alterations of the ionic currents. LPS-treated, EXCB-treated, and control LA myocytes exhibited similar Na⁺ currents. In addition, the LPS-treated LA myocytes exhibited a lower [Ca] content and higher sarcoplasmic reticulum calcium content, than the controls. EXCB reversed the LPS-induced calcium alterations. In conclusion, EXCB modulates LPS-induced LA electrophysiological characteristics and calcium homeostasis, which may contribute to attenuating LPS-induced arrhythmogenesis.
由败血症引起的严重细菌感染总会导致深刻的生理变化，包括发热、低血压、心律失常、组织坏死、全身多器官功能障碍，最终导致死亡。脂多糖（LPS）在败血症情况下会引发炎症反应，这可能会增加心律失常的倾向。Excavatolide B（EXCB）具有强大的抗炎作用。然而，尚不清楚EXCB是否能调节心房肌细胞的电生理特性和钙稳态。本研究调查了EXCB对暴露于脂多糖的心房肌细胞的影响。采用全细胞膜片钳和indo-1荧光比率技术记录单个分离的兔左心房（LA）心肌细胞的动作电位（AP）、离子电流和细胞内钙（[Ca]），分别给予和不给予LPS（1μg/mL）以及LPS + EXCB（10μM）处理6±1小时，以研究EXCB在心房电生理中的作用。在存在LPS的情况下，与LPS处理的细胞（n = 12）相比，EXCB处理的LA心肌细胞（n = 13）在动作电位持续时间的20%（29±2 vs. 20±2 ms，P < 0.05）、50%（52±4 vs. 40±3 ms，P < 0.05）和90%（85±5 vs. 68±3 ms，P < 0.05）时更长。LPS处理的LA心肌细胞与对照LA心肌细胞相比，显示出更高的晚钠电流、钠/钙交换电流、瞬时外向电流和延迟整流钾电流，但L型钙电流更低。EXCB处理可逆转LPS诱导的离子电流变化。LPS处理、EXCB处理和对照LA心肌细胞表现出相似的钠电流。此外，LPS处理的LA心肌细胞与对照相比，表现出更低的[Ca]含量和更高的肌浆网钙含量。EXCB可逆转LPS诱导的钙变化。总之，EXCB调节LPS诱导的LA电生理特性和钙稳态，这可能有助于减轻LPS诱导的心律失常。
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