title: Latrunculin B modulates electrophysiological characteristics and arrhythmogenesis in pulmonary vein cardiomyocytes.
abstract: AF (atrial fibrillation) is the most common sustained arrhythmia, and the PVs (pulmonary veins) play a critical role in triggering AF. Stretch causes structural remodelling, including cytoskeleton rearrangement, which may play a role in the genesis of AF. Lat-B (latrunculin B), an inhibitor of actin polymerization, is involved in Ca(2+) regulation. However, it is unclear whether Lat-B directly modulates the electrophysiological characteristics and Ca(2+) homoeostasis of the PVs. Conventional microelectrodes, whole-cell patch-clamp, and the fluo-3 fluorimetric ratio technique were used to record ionic currents and intracellular Ca(2+) within isolated rabbit PV preparations, or within isolated single PV cardiomyocytes, before and after administration of Lat-B (100 nM). Langendorff-perfused rabbit hearts were exposed to acute and continuous atrial stretch, and we studied PV electrical activity. Lat-B (100 nM) decreased the spontaneous electrical activity by 16±4% in PV preparations. Lat-B (100 nM) decreased the late Na(+) current, L-type Ca(2+) current, Na(+)/Ca(2+) exchanger current, and stretch-activated BKCa current, but did not affect the Na(+) current in PV cardiomyocytes. Lat-B reduced the transient outward K(+) current and ultra-rapid delayed rectifier K(+) current, but increased the delayed rectifier K(+) current in isolated PV cardiomyocytes. In addition, Lat-B (100 nM) decreased intracellular Ca(2+) transient and sarcoplasmic reticulum Ca(2+) content in PV cardiomyocytes. Moreover, Lat-B attenuated stretch-induced increased spontaneous electrical activity and trigger activity. The effects of Lat-B on the PV spontaneous electrical activity were attenuated in the presence of Y-27632 [10 μM, a ROCK (Rho-associated kinase) inhibitor] and cytochalasin D (10 μM, an actin polymerization inhibitor). In conclusion, Lat-B regulates PV electrophysiological characteristics and attenuates stretch-induced arrhythmogenesis.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Sijhih Cathay General Hospital, New Taipei City, Taiwan School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Yen-Yu
authors.initials: YY
authors.lastname: Lu
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yung-Kuo
authors.initials: YK
authors.lastname: Lin
authors.affiliation: Department of Marine Biotechnology and Resources, Asia-Pacific Ocean Research Center, National Sun Yat-sen University, Kaohsiung, Taiwan.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Wen
authors.affiliation: Department of Biomedical Engineering, National Defense Medical Center, Taipei, Taiwan bme02@mail.ndmctsgh.edu.tw.
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chen
authors.affiliation: National Yang-Ming University, School of Medicine; Division of Cardiology and Cardiovascular Research Center, Veterans General Hospital-Taipei, Taipei, Taiwan.
authors.forename: Shih-Ann
authors.initials: SA
authors.lastname: Chen
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Chen
mesh_terms: D000577:Amides / Q000494:pharmacology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000503:physiopathology*; D001281:Atrial Fibrillation / Q000150:complications / Q000503:physiopathology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects; D015638:Cytochalasin D / Q000494:pharmacology; D055724:Electrophysiological Phenomena / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D010477:Perfusion; D011667:Pulmonary Veins / Q000473:pathology*; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D053778:Thiazolidines / Q000494:pharmacology*
chemical_list: D000577:Amides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D011725:Pyridines; D019831:Sodium-Calcium Exchanger; D053778:Thiazolidines; C110374:sodium-calcium exchanger 1; C108830:Y 27632; D015638:Cytochalasin D; C037068:latrunculin B
keywords: atrial fibrillation; latrunculin B; pulmonary veins; stretch