【作者】 宋艳东；

【导师】 顾忠伟； 杨新春；

【作者基本信息】 中国协和医科大学 ， 药物化学， 2005， 博士

【摘要】 起源于右心室流出道的室性心律失常，通常发生在无器质性心脏病的人身上。大部分这种室性心律失常可以通过射频消融右心室流出道而治愈，因此具有较好的预后。然而，引发右心室流出道室性心律失常的离子机制还不清楚。我们研究的目的是揭示右心室流出道的电生理特性并探讨右心室流出道致室性心律失常的机制。 应用常规微电极技术，我们在右心室流出道（RVOT）心肌细胞记录到三种类型的动作电位：自律性慢反应动作电位、非自律性慢反应动作电位和非自律性快反应动作电位。因此，RVOT心肌细胞表现出明显的动作电位时程（APD）的离散。同时，在RVOT心肌细胞，没有诱发因素存在的条件下，我们记录到早后除极化（EAD）和迟后除极化（DAD）。而在右心室（RV）心肌细胞只记录到典型的快反应动作电位，没有记录到EAD和DAD。 应用全细胞膜片钳制技术，我们首次报道了在兔的心室肌细胞存在一种电压依赖性的非特异性阳离子流（NSCC）。这种非特异性阳离子通道对Na⁺，K⁺，Cs⁺均可通透，可被GdCl₃阻断，并对细胞外液的Ca²⁺、Mg²⁺及胰岛素敏感。从灌流液中去除Ca²⁺、Mg²⁺或在灌流液中加入胰岛素均可激活NSCC，而使NSCC的内外向电流均变大。 NSCC分布于RV所有的心肌细胞，但在RVOT的某些心肌细胞，NSCC很小甚至缺如。在这类心肌细胞中，与很小的NSCC相对应的是APD很长，并可在无诱发因素存在时记录到EAD。当用激动剂激活NSCC时，动作电位的平台相缩短，EAD消失。另外，I_TO在两部位的电流密度有所不同，而I_KI和I_K的电流密度在RVOT和RV这两个部位没有显著差异。 我们的研究首次表明，右心室流出道某些心肌细胞具有自律性；而另一些细胞可自发产生EAD和DAD。在右心室流出道室性心律失常的发生机制中，EAD可能起重要作用。而增大的APD的离散度，可以产生折返性室性心律失常。更多还原

【Abstract】 Right ventricular outflow tract （RVOT） has been proved as an important source in the initiation of ventricular arrhythmias. Many evidences have been reported that ventricular arrhythmias originated from RVOT in individuals without any heart diseases. However, the underlying ionic mechanisms of ventricular arrhythmias originated from RVOT remain unclear. The purpose of this study was to disclose the ionic basis of such arrhythmia.Using conventional microelectrode technique, three different AP types in RVOT were recorded: pace-making action potentials; slow response action potentials; and fast response action potentials. Then, significant dispersion in APD occurred in this location of right ventricle of rabbit heart. EAD and DAD can be recorded in right ventricular outflow tract without any inducement.Using the whole-cell patch-clamp technique, clear evidence was provided for the existence of a hitherto unreported, voltage-dependent nonselective cation current （NSCC） in rabbit ventricular myocytes. Na⁺, K⁺, Cs⁺ can permeate through the channel and the nonselective cation current can be blocked by Gd³⁺.They were sensitive to Ca²⁺,Mg²⁺-free and insulin in bathing solution. Depleting of Ca²⁺and Mg²⁺ in the bathing solution can increase the amplitudes of this outward current. Insulin (with normal concentration of Ca²⁺and Mg²⁺ in Tyrode’s solution) can also increase the amplitude of NSCC.The amplitude of I_To in different group is markedly different while I_k1 and I_k have not significant difference between the two areas. NSCC distributed in all of the cells in right ventricle. But the amplitude of this current is significantly less in some right ventricular outflow tract myocytes, or even lacking. Corresponding to this the action更多还原