Optical mapping of V(m) and Ca(i)(2+) in a model of arrhythmias induced by local catecholamine application in patterned cell cultures.
Optical mapping of V(m) and Ca(i)(2+) in a model of arrhythmias induced by local catecholamine application in patterned cell cultures.
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在图案化细胞培养物中局部应用儿茶酚胺诱导的心律失常模型中 V(m) 和 Ca(i)(2 ) 的光学图谱。
DOI：
10.1007/s00424-006-0162-6
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Fast,VladimirG
中科院分区：
文献类型：
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作者：
Lan,DavidZ;Pollard,AndrewE;Knisley,StephenB;Fast,VladimirG
已知儿茶酚胺可引起心律失常，但重要方面如心律失常源在多细胞组织中的定位和确切的离子机制尚不清楚。在这项工作中，开发了一个多细胞模型的心律失常引起的局部肾上腺素的应用;Vmand Cai 2+的变化，在心律失常的来源进行了测量，使用荧光染料和高分辨率的光学映射。通过模式化生长产生新生大鼠肌细胞的培养链（宽度约0.4mm）。通过两个微量移液器在0.3-0.6 mm的区域上施加肾上腺素（1 μmol/l），并通过短阵起搏刺激股线。局部应用肾上腺素引起触发性心律失常，16例中有9例的周期长度为202-379 ms，持续时间>10 s。OpticalVmmapping显示，在78%的病例中，心律失常源位于局部灌注区的边界。用Ca 2+敏感染料Fluo-4染色在大多数情况下（85%）防止了心律失常诱导，这可能是由于染料的Ca 2+缓冲。光学Cai ~（2+）标测显示，45%的病例在局部灌注区的边界处存在非传播Cai ~（2+）振荡。总之，我们开发了一种新的模型，儿茶酚胺依赖性心律失常允许映射ofVMand Cai 2+在心律失常源与显微分辨率。心律失常通常起源于肾上腺素灌注区的边界。心律失常源的位置与局部Cai 2+振荡相关，表明心律失常是由这些位置的Cai 2+过载引起的。
Catecholamines are known to provoke cardiac arrhythmias, but important aspects such as localization of the arrhythmia source in multicellular tissue and exact ionic mechanisms are not well-known. In this work, a multicellular model of arrhythmias caused by local epinephrine application was developed;Vmand Cai2+changes at the arrhythmia source were measured using fluorescent dyes and high-resolution optical mapping. Cultured strands of neonatal rat myocytes (width ~0.4 mm) were produced by patterned growth. Epinephrine (1 μmol/l) was applied over an area of 0.3–0.6 mm via two micropipettes, and strands were stimulated by burst pacing. Local epinephrine application caused triggered arrhythmias with cycle lengths of 202–379 ms and duration of >10 s in 9 out of 16 preparations. OpticalVmmapping demonstrated that in 78% of cases, the source of arrhythmia was located at the boundary of the locally perfused area. Staining with Cai2+-sensitive dye Fluo-4 prevented arrhythmia induction in most cases (85%) likely due to Ca2+buffering by the dye. Optical Cai2+mapping revealed non-propagated Cai2+oscillations at the boundary of the locally perfused area in 45% cases. In conclusion, we developed a new model of catecholamine-dependent arrhythmias allowing mapping ofVmand Cai2+at the arrhythmia source with microscopic resolution. The arrhythmias typically originated from the boundary of the epinephrine-perfused area. The location of the arrhythmia source correlated with localized Cai2+oscillations suggesting that arrhythmias were caused by Cai2+overload at these locations.