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Arrhythmogenic ion-channel remodeling in the heart: heart failure, myocardial infarction, and atrial fibrillation.

机译:心脏中导致心律失常的离子通道重塑:心力衰竭,心肌梗塞和心房颤动。

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Rhythmic and effective cardiac contraction depends on appropriately timed generation and spread of cardiac electrical activity. The basic cellular unit of such activity is the action potential, which is shaped by specialized proteins (channels and transporters) that control the movement of ions across cardiac cell membranes in a highly regulated fashion. Cardiac disease modifies the operation of ion channels and transporters in a way that promotes the occurrence of cardiac rhythm disturbances, a process called "arrhythmogenic remodeling." Arrhythmogenic remodeling involves alterations in ion channel and transporter expression, regulation and association with important protein partners, and has important pathophysiological implications that contribute in major ways to cardiac morbidity and mortality. We review the changes in ion channel and transporter properties associated with three important clinical and experimental paradigms: congestive heart failure, myocardial infarction, and atrial fibrillation.We pay particular attention to K+, Na+, and Ca2+ channels; Ca2+ transporters; connexins; and hyperpolarization-activated nonselective cation channels and discuss the mechanisms through which changes in ion handling processes lead to cardiac arrhythmias. We highlight areas of future investigation, as well as important opportunities for improved therapeutic approaches that are being opened by an improved understanding of the mechanisms of arrhythmogenic remodeling.
机译:节律性和有效的心脏收缩取决于适当定时的心脏电活动的产生和扩散。这种活动的基本细胞单位是动作电位,它由专门的蛋白质(通道和转运蛋白)形成,这些蛋白质以高度受控的方式控制离子在心脏细胞膜上的移动。心脏疾病以促进心律失常发生的方式改变了离子通道和转运蛋白的运作,这一过程称为“心律失常重塑”。心律失常重塑涉及离子通道和转运蛋白表达的改变,调控以及与重要蛋白质伴侣的缔合,并且具有重要的病理生理意义,其以主要方式对心脏发病率和死亡率做出贡献。我们回顾了与三个重要的临床和实验范例相关的离子通道和转运蛋白特性的变化:充血性心力衰竭,心肌梗塞和心房颤动。我们特别注意K +,Na +和Ca2 +通道; Ca2 +转运蛋白;连接蛋白和超极化激活的非选择性阳离子通道,并讨论离子处理过程变化导致心律不齐的机制。我们重点介绍了未来的研究领域,以及通过对心律失常重塑机制的进一步了解而打开的改进治疗方法的重要机会。

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