Ischaemia-induced sarcolemmal changes and their role in Ins(1,4,5)P3 generation and arrhythmogenesis

贝克心脏研究所实验室过去几年的研究发现了一种导致心律失常的新机制，心律失常是心力衰竭和急性心脏病发作时因血流急剧减少而导致心源性猝死的主要原因。血流量的减少会导致氧气和营养物质的减少，因此跳动的心脏细胞没有足够的能量来适当地维持功能。在这些应激条件下，心肌细胞会产生大量名为IP3的小分子，这种小分子会干扰细胞的正常电平衡。阻断IP3的产生可防止在这些急性缺血条件下发生心律失常。在最近的研究中，我们已经确定了许多负责在心脏细胞中产生IP3的酶，并定义了负责这一反应的细胞区域的属性。我们现在想要确切地确定一段时间的缺血是如何改变酶的定位或功能的，这些酶是导致这种导致致命心律失常的病理变化的。

Studies in our laboratory at the Baker Heart Research Institute over the last several years have identified a novel mechanism causing the development of arrhythmias, a primary cause of sudden cardiac death in heart failure as well as during an acute heart attack caused by acutely reduced blood flow. The reduced blood flow leads to lowered oxygen and nutrients and thus the beating heart cells have insufficient energy to properly maintain function. Under these stressed conditions, cardiac myocytes produce large amounts of a small molecule called IP3, which interferes with the normal electrical balance of the cells. Blocking IP3 generation prevents arrhythmias under these acutely ischaemic conditions. In more recent studies, we have identified many of the enzymes responsible for generation of IP3 in heart cells and have defined the properties of the regions of the cell responsible for this response. We now want to establish exactly how a period of ischaemia alters the localization or functioning of the enzymes that are responsible for this pathological change that leads to fatal arrhythmias.