The role of mechanoelectric feedback in cardiac arrhythmogenesis

心律失常是心脏正常电节律的中断，并且可以从无症状到致命。过去人们认为，心肌的电功能和机械功能基本上是分开的：电活动触发收缩，就像扣动扳机一样-一旦事件开始，电事件就不再起作用。然而，近年来，这显然是对真实的情况的过分简单化。事实上，心脏的电活动受到心肌拉伸的程度和时间的强烈影响，这一过程称为机电反馈。由于它可以在孤立的组织中证明，机械电反馈必须是心肌的固有特性。在离体心脏制备中已经显示，被动牵张在正常动作电位形状和传播中产生电干扰，并且这些电干扰可能足够强大以产生严重心律失常。人类疾病中有嗜铬细胞。例如，房性心律失常在老年人中很常见，似乎这可能是由于高血压导致的心房慢性牵张所致。此外，在那些从心脏病发作中恢复的患者中，心肌的受损部分似乎可能使周围组织受到不寻常的机械应力，并可能引发心律失常。本研究旨在探讨这种机械电反馈的机制，试图了解某些类型的心律失常。利用分子生物学技术，我们将研究一种新型的牵张激活钾通道在健康和患病动物心脏中的基因表达，目的是观察这些通道表达水平的变化是否与心脏对牵张反应的变化相关。

Arrhythmias are disruptions of the normal electrical rhythm of the heart, and can vary from asymptomatic to fatal. It used to be thought that the electrical and mechanical functions of the heart muscle were essentially separate: the electrical activity triggered contraction something like pulling the trigger of a gun- once events were in motion, the electrical events played no further role. However, in recent years it has become apparent that this is an over-simplification of the real situation. In fact, the electrical activity of the heart is influenced strongly by the degree and timing of stretch to which the heart muscle is subjected, a process called Mechano-electric feedback. Since it can be demonstrated in isolated tissues, mechano-electric feedback must be an intrinsic property of the heart muscle. It has been shown in isolated heart preparations that passive stretch produces electrical disturbances in the normal action potential shape and propagation and that these electrical disturbances can be powerful enough to generate severe arrhythmias. There are paralells in human diseases. For example, atrial arrhythmias are common in older people, and it seems that these may be due to chronic stretch of the atria, as a consequence of high blood pressure. In addition, in those patients recovering from a heart attack, it seems likely that the damaged part of the heart muscle subjects the surrounding tissue to unusual mechanical stresses, and may trigger arrhythmias. This project aims to investigate the mechanisms underlying this mechano-electric feedback, in an attempt to understand some types of arrhythmias. Using molecular biology techniques, we will look at the gene expression of a novel type of stretch-activated potassium channel in both healthy and diseased animal hearts, with the aim of seeing if changes in the level of expression of these channels is correlated with changes in the response of the heart to stretch.