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Excavatolide B Modulates the Electrophysiological Characteristics and Calcium Homeostasis of Atrial Myocytes

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 incr...

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Autores principales: Hwang, Hwong-Ru, Tai, Buh-Yuan, Cheng, Pao-Yun, Chen, Ping-Nan, Sung, Ping-Jyun, Wen, Zhi-Hong, Hsu, Chih-Hsueng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5334606/
https://www.ncbi.nlm.nih.gov/pubmed/28125029
http://dx.doi.org/10.3390/md15020025
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author Hwang, Hwong-Ru
Tai, Buh-Yuan
Cheng, Pao-Yun
Chen, Ping-Nan
Sung, Ping-Jyun
Wen, Zhi-Hong
Hsu, Chih-Hsueng
author_facet Hwang, Hwong-Ru
Tai, Buh-Yuan
Cheng, Pao-Yun
Chen, Ping-Nan
Sung, Ping-Jyun
Wen, Zhi-Hong
Hsu, Chih-Hsueng
author_sort Hwang, Hwong-Ru
collection PubMed
description 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(2+)](i)) 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 (n = 13) had a longer AP duration at 20% (29 ± 2 vs. 20 ± 2 ms, p < 0.05), 50% (52 ± 4 vs. 40 ± 3 ms, p < 0.05), and 90% (85 ± 5 vs. 68 ± 3 ms, p < 0.05), compared to the LPS-treated cells (n = 12). LPS-treated LA myocytes showed a higher late sodium current, Na(+)/Ca(2+) exchanger current, transient outward current, and delayed rectifier potassium current, but a lower l-type Ca(2+) 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(2+)](i) 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.
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spelling pubmed-53346062017-03-16 Excavatolide B Modulates the Electrophysiological Characteristics and Calcium Homeostasis of Atrial Myocytes Hwang, Hwong-Ru Tai, Buh-Yuan Cheng, Pao-Yun Chen, Ping-Nan Sung, Ping-Jyun Wen, Zhi-Hong Hsu, Chih-Hsueng Mar Drugs Article 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(2+)](i)) 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 (n = 13) had a longer AP duration at 20% (29 ± 2 vs. 20 ± 2 ms, p < 0.05), 50% (52 ± 4 vs. 40 ± 3 ms, p < 0.05), and 90% (85 ± 5 vs. 68 ± 3 ms, p < 0.05), compared to the LPS-treated cells (n = 12). LPS-treated LA myocytes showed a higher late sodium current, Na(+)/Ca(2+) exchanger current, transient outward current, and delayed rectifier potassium current, but a lower l-type Ca(2+) 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(2+)](i) 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. MDPI 2017-01-24 /pmc/articles/PMC5334606/ /pubmed/28125029 http://dx.doi.org/10.3390/md15020025 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hwang, Hwong-Ru
Tai, Buh-Yuan
Cheng, Pao-Yun
Chen, Ping-Nan
Sung, Ping-Jyun
Wen, Zhi-Hong
Hsu, Chih-Hsueng
Excavatolide B Modulates the Electrophysiological Characteristics and Calcium Homeostasis of Atrial Myocytes
title Excavatolide B Modulates the Electrophysiological Characteristics and Calcium Homeostasis of Atrial Myocytes
title_full Excavatolide B Modulates the Electrophysiological Characteristics and Calcium Homeostasis of Atrial Myocytes
title_fullStr Excavatolide B Modulates the Electrophysiological Characteristics and Calcium Homeostasis of Atrial Myocytes
title_full_unstemmed Excavatolide B Modulates the Electrophysiological Characteristics and Calcium Homeostasis of Atrial Myocytes
title_short Excavatolide B Modulates the Electrophysiological Characteristics and Calcium Homeostasis of Atrial Myocytes
title_sort excavatolide b modulates the electrophysiological characteristics and calcium homeostasis of atrial myocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5334606/
https://www.ncbi.nlm.nih.gov/pubmed/28125029
http://dx.doi.org/10.3390/md15020025
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