Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, the Second Hospital of Tianjin Medical University, Tianjin, China.
Laboratory of Cardiovascular Physiology, Li Ka Shing Institute of Health Sciences, Hong Kong, China.
Clin Exp Pharmacol Physiol. 2020 Dec;47(12):1932-1942. doi: 10.1111/1440-1681.13385. Epub 2020 Aug 16.
Higher sympathetic activity predisposes to malignant ventricular arrhythmias in the context of myocardial infarction (MI). This is, in part, mediated by the electrical activity of the stellate ganglion (SG). The aim of this study is to examine the effects of ticagrelor pretreatment on the electrophysiological properties of SG neurons following MI in rabbits. MI was induced by isoproterenol (ISO) of 150 mg kg d (twice at an interval of 24 hours). Ticagrelor pretreatment was administered at low- (10 mg kg d) or high-dose (20 mg kg d). Protein and RNA expression were determined by immunohistochemical analysis and real-time PCR, respectively. The activity of sodium channel current (I), delayed rectifier potassium current (I), M-type potassium current (I) as well as action potentials (APs) from SG neurons were measured by whole-cell patch-clamp. Intracellular calcium concentrations were measured by confocal microscopy. Compared with the control group, the MI group exhibited a greater amplitude of I, I and I, significantly altered activation and inactivation characteristics of I, no significant alterations in protein or mRNA expression of sodium and M-type potassium channels, along with higher AP amplitude and frequency and intracellular calcium concentrations. Most of these abnormalities were prevented by pretreatment with low- or high-dose ticagrelor. Our data suggest that ticagrelor exerts cardioprotective effects, potentially through modulating the activity of different ion channels in SG neurons.
较高的交感神经活动易导致心肌梗死（MI）时发生恶性室性心律失常。这部分是通过星状神经节（SG）的电活动介导的。本研究旨在研究替格瑞洛预处理对兔 MI 后 SG 神经元电生理特性的影响。MI 通过异丙肾上腺素（ISO）诱导，剂量为 150mg/kg/d（间隔 24 小时两次）。替格瑞洛预处理以低剂量（10mg/kg/d）或高剂量（20mg/kg/d）给药。通过免疫组织化学分析和实时 PCR 分别测定蛋白质和 RNA 表达。通过全细胞膜片钳测量 SG 神经元的钠通道电流（I）、延迟整流钾电流（I）、M 型钾电流（I）和动作电位（AP）。通过共聚焦显微镜测量细胞内钙浓度。与对照组相比，MI 组 I、I 和 I 的幅度更大，I 的激活和失活特性明显改变，钠和 M 型钾通道的蛋白或 mRNA 表达无明显变化，AP 幅度和频率以及细胞内钙浓度升高。这些异常大部分通过低剂量或高剂量替格瑞洛预处理得到预防。我们的数据表明，替格瑞洛发挥心脏保护作用，可能通过调节 SG 神经元中不同离子通道的活性。
