The role of mechanoelectric feedback in cardiac arrhythmogenesis

心律失常是心脏正常电节律的中断，从无症状到致命都有可能。过去人们认为，心肌的电功能和机械功能本质上是分开的：电活动触发收缩，就像扣动扳机一样——一旦活动开始，电活动就不再起作用了。然而，近年来很明显，这是对实际情况的过度简化。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，这一过程被称为机电反馈。因为它可以在孤立的组织中被证明，机电反馈一定是心肌的内在特性。在离体心脏制剂中已经证明，被动拉伸对正常动作电位的形状和传播产生电干扰，这些电干扰足以产生严重的心律失常。人类疾病也有类似的情况。例如，心房心律失常在老年人中很常见，这似乎是由于高血压引起的心房慢性拉伸。此外，在那些从心脏病发作中恢复的患者中，心肌受损的部分似乎可能使周围组织承受不寻常的机械压力，并可能引发心律失常。本项目旨在研究这种机电反馈的机制，试图理解某些类型的心律失常。利用分子生物学技术，我们将观察健康和患病动物心脏中一种新型拉伸激活钾通道的基因表达，目的是观察这些通道表达水平的变化是否与心脏对拉伸反应的变化相关。

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.