Genetic and molecular basis of cardiac arrhythmias: impact on clinical management part III.
Genetic and molecular basis of cardiac arrhythmias: impact on clinical management part III.
复制标题
心律失常的遗传和分子基础：对临床管理的影响第三部分。
作者：
S. Priori;J. Barhanin;R. Hauer;W. Haverkamp;H. Jongsma;A. Kleber;W. McKenna;D. Roden;Y. Rudy;K. Schwartz;P. Schwartz;J. Towbin;A. Wilde
在本文的第一部分和第二部分，我们讨论了单基因遗传病。这些都是由一个先天的改变决定或支持的，并且在大多数情况下以单一的遗传改变为特征。这允许使用“范例”;即，疾病，例如长QT综合征（LQTS），其中可以追踪离子通道基因上的特定突变到其在患者中的电生理后果。不幸的是，对于执业心脏病专家来说，这些“简单”疾病仅构成与心律失常相关的临床病症的一小部分。大多数病例影响的患者的致瘤底物是复杂的。事实上，负责正常和异常电活动的分子系统的表达显著变化，这取决于多种因素，包括年龄、区域因素（细胞类型、心肌灌注）和诸如心脏肥大、心肌梗死和心力衰竭的潜在慢性疾病。
研究这种相互作用的分子功能的复杂系统需要一种与考虑单基因疾病所需的方法有些不同的方法。因此，在本节中，我们将讨论更广泛的主题，这些主题对于理解多细胞网络中基因表达、离子通道功能和细胞偶联的整合至关重要，这是理解更频繁和更复杂的致瘤条件的第一步。
#心脏基因表达的多样性
了解心脏动作电位形状的细胞间变异性和冲动传播的机制是了解正常和异常心脏电生理的关键。这种变异性大部分可归因于个体离子电流特征的变异性，其综合行为决定了个体心脏细胞中动作电位的形状和持续时间，以及细胞间通讯的变异性。离子电流现在被认为是流经特定的成孔膜蛋白，称为离子通道。第一个编码离子通道蛋白的基因是...
In Parts I and II of this article,* we discussed monogenic arrhythmic disorders. These are determined or favored by an inborn alteration and for the most part are characterized by a single genetic alteration. This has allowed the use of “paradigms”; namely, diseases, such as the long-QT syndrome (LQTS), in which it has been possible to trace specific mutations on ion channel genes to their electrophysiological consequences in the patient. Unfortunately for the practicing cardiologist, these “simple” diseases constitute only a small part of the clinical conditions associated with cardiac arrhythmias. The majority of cases affect patients in whom the arrhythmogenic substrate is complex. Indeed, the expression of the molecular systems responsible for normal and abnormal electrical activity vary significantly, depending on a variety of factors, including age, regional factors (type of cells, myocardial perfusion), and such underlying chronic diseases as cardiac hypertrophy, myocardial infarction, and heart failure.
The study of this complex system of interacting molecular functions requires an approach somewhat different from that required to consider monogenic disease. Accordingly, in this section we discuss broader themes that are essential to understand the integration of gene expression, ion channel function, and cell coupling in multicellular networks as a first step toward the comprehension of more frequent and more complex arrhythmogenic conditions.
### Diversity of Gene Expression in the Heart
Understanding cell-to-cell variability in the cardiac action potential shape and the mechanisms underlying impulse propagation is the key to understanding normal and abnormal cardiac electrophysiology. Much of this variability can be attributed to variability in the characteristics of individual ion currents whose integrated behavior determines the shape and duration of action potentials in individual cardiac cells, as well as to variability in cell-to-cell communications. Ion currents are now recognized to flow through specific pore-forming membrane proteins called ion channels. The first gene encoding an ion channel protein was …
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影响因子：
20.1
作者：
Dixon, JE;Shi, WM;McKinnon, D
通讯作者：
McKinnon, D
Anti-minK 反义降低了快速激活的心脏延迟整流 K 电流的幅度。
影响因子：
20.1
作者：
Yang,T;Kupershmidt,S;Roden,DM
通讯作者：
Roden,DM
影响因子：
20.1
作者：
DIXON, JE;MCKINNON, D
通讯作者：
MCKINNON, D
影响因子：
15.9
作者：
Guerrero, PA;Schuessler, RB;Saffitz, JE
通讯作者：
Saffitz, JE
DOI：
10.1126/science.2176745
发表时间：
1990
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Yue,DT;Backx,PH;Imredy,JP
通讯作者：
Imredy,JP