Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, SP, Brasil.
Arq Bras Cardiol. 2020 Apr;114(4):732-735. doi: 10.36660/abc.20190220. Epub 2020 May 29.
Ranolazine (RANO) prevents cardiac arrhythmia by blocking the late sodium current (INaL). A transmural gradient of Nav1.5 is found in the left ventricular wall of the heart. Thus, we investigated the effects of RANO in healthy cardiomyocytes and in a cellular model of type 3 long QT syndrome (LQT3). We used isolated endocardium (ENDO) and epicardium (EPI) cells and a video edge detection system and fluorescence microscopy to monitor calcium transients. RANO (0.1, 1, 10 and 30 uM, at 25oC) at a range of pacing frequencies showed a minor impact on both cell types, but RANO at 30uM and 35oC for ENDO cells attenuated sarcomere shortening by~21%. Next, to mimic LQT3, we exposed ENDO and EPI cells to anemone toxin II (ATX-II), which augments INaL. Cellular arrhythmias induced by ATX-II were abrogated by RANO (30 µM) at 35oC. Based on our results we can conclude that RANO has a minor impact on sarcomere shortening of healthy ENDO and EPI cells and it abrogates arrhythmias induced by INaLto a similar level in ENDO and EPI cells.
雷诺嗪（ RANO ）通过阻断晚期钠电流（ INaL ）预防心律失常。在心脏左心室壁中发现 Nav1.5 的跨壁梯度。因此，我们研究了雷诺嗪在健康心肌细胞和 3 型长 QT 综合征（ LQT3 ）的细胞模型中的作用。我们使用分离的心内膜（ ENDO ）和心外膜（ EPI ）细胞以及视频边缘检测系统和荧光显微镜来监测钙瞬变。雷诺嗪（ 0.1 、 1 、 10 和 30 μ M ，在 25°C ）在一系列起搏频率下对两种细胞类型的影响都较小，但雷诺嗪在 30 μ M 和 35°C 下对 ENDO 细胞的肌节缩短作用减弱了约 21% 。接下来，为了模拟 LQT3 ，我们用海葵毒素 II （ ATX-II ）处理 ENDO 和 EPI 细胞，该毒素增强 INaL 。 ATX-II 诱导的细胞心律失常被雷诺嗪（ 30 μ M ）在 35°C 时消除。基于我们的结果，我们可以得出结论，雷诺嗪对健康 ENDO 和 EPI 细胞的肌节缩短的影响较小，并且在 ENDO 和 EPI 细胞中，它以相似的水平消除了 INaL 诱导的心律失常。
