title: Excavatolide B Modulates the Electrophysiological Characteristics and Calcium Homeostasis of Atrial Myocytes.
abstract: 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 ([Ca2+]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⁺/Ca2+exchanger current, transient outward current, and delayed rectifier potassium current, but a lower l-type Ca2+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 [Ca2+]icontent 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.
authors.affiliation: Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 804, Taiwan. hwang.lin@msa.hinet.net.|Division of Cardiology, Department of Medicine, E-Da Hospital, Kaohsiung 824, Taiwan. hwang.lin@msa.hinet.net.|Division of Cardiology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan. hwang.lin@msa.hinet.net.
authors.forename: Hwong-Ru
authors.initials: HR
authors.lastname: Hwang
authors.affiliation: Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 804, Taiwan. tai1337@hotmail.com.|Department of Traditional Medicine, Jianan Mental Hospital, Tainan 717, Taiwan. tai1337@hotmail.com.
authors.forename: Buh-Yuan
authors.initials: BY
authors.lastname: Tai
authors.affiliation: Department of Physiology and Biophysics and Graduate Institute of Physiology, National Defense Medical Center, Taipei 114, Taiwan. pycheng@mail.ndmctsgh.edu.tw.
authors.forename: Pao-Yun
authors.initials: PY
authors.lastname: Cheng
authors.affiliation: Department of Biomedical Engineering, National Defense Medical Center, Taipei 114, Taiwan. g931310@mail.ndmctsgh.edu.tw.
authors.forename: Ping-Nan
authors.initials: PN
authors.lastname: Chen
authors.affiliation: National Museum of Marine Biology and Aquarium, Pingtung 944, Taiwan. pjsung@nmmba.gov.tw.|Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung 404, Taiwan. pjsung@nmmba.gov.tw.|Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan. pjsung@nmmba.gov.tw.
authors.forename: Ping-Jyun
authors.initials: PJ
authors.lastname: Sung
authors.affiliation: Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 804, Taiwan. wzh@mail.nsysu.edu.tw.|Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University and Academia Sinica, Kaohsiung 804, Taiwan. wzh@mail.nsysu.edu.tw.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Wen
authors.affiliation: Division of Cardiology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan. jhon10298@gmail.com.
authors.forename: Chih-Hsueng
authors.initials: CH
authors.lastname: Hsu
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004224:Diterpenes / Q000494:pharmacology*; D055724:Electrophysiological Phenomena / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects*; D007211:Indoles / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
chemical_list: D004224:Diterpenes; D007211:Indoles; D008070:Lipopolysaccharides; C574336:excavatolide B; D012964:Sodium; C048960:indo-1; D002118:Calcium
keywords: calcium regulation; cardiomyocyte; ionic currents; left atrium; sepsis