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

缺血引起的肌膜变化及其在 Ins(1,4,5)P3 生成和心律失常发生中的作用

• 批准号: nhmrc : 317802
• 负责人: A/Pr Elizabeth Woodcock
• 金额: $ 31.26万
• 依托单位: Baker IDI Heart and Diabetes Institute
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2005
• 资助国家: 澳大利亚
• 起止时间: 2005-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/ischaemia-induced-sarcolemmal-generation-arrhythmogenesis/96116
• 关键词: Ischaemia; induced; sarcolemmal; changes; their

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.

过去几年，贝克心脏研究所实验室的研究已经确定了一种导致心律失常发生的新机制，心律失常是心力衰竭以及因血流量急剧减少而引起的急性心脏病发作期间心源性猝死的主要原因。血流减少导致氧气和营养物质减少，因此跳动的心脏细胞没有足够的能量来维持正常功能。在这些应激条件下，心肌细胞产生大量称为IP3的小分子，干扰细胞的正常电平衡。阻断IP3的产生可预防这些急性缺血条件下的心律失常。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，并确定了负责这种反应的细胞区域的特性。我们现在想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，这些酶是导致致命性心律失常的病理变化的原因。