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 Ca2+ regulation. However, it is unclear whether Lat-B directly modulates the electrophysiological characteristics and Ca2+ 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 Ca2+ 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 Ca2+ current, Na+/Ca2+ 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 Ca2+ transient and sarcoplasmic reticulum Ca2+ 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.
Latrunculin B modulates electrophysiological characteristics and arrhythmogenesis in pulmonary vein cardiomyocytes
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Yen-Yu Lu, Yung-Kuo Lin, Zhi-Hong Wen, Yao-Chang Chen, Shih-Ann Chen, Yi-Jen Chen; Latrunculin B modulates electrophysiological characteristics and arrhythmogenesis in pulmonary vein cardiomyocytes. Clin Sci (Lond) 1 May 2016; 130 (9): 721–732. doi: https://doi.org/10.1042/CS20150593
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