How does the mitochondria regulate cardiac L-type Ca2+ channel function?

线粒体如何调节心脏L型Ca2通道功能？

• 批准号: nhmrc : 404002
• 负责人: A/Pr Livia Hool
• 金额: $ 21.89万
• 依托单位: The University of Western Australia
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/does-mitochondria-regulate-channel-function/80930
• 关键词: How; does; mitochondria; regulate; cardiac

Oxygen is vital to cellular metabolism and function. Oxygen delivery to cells is critical and a lack of oxygen such as occurs during a heart attack can be lethal. The L-type Ca2+ channel is a protein in the membrane of heart muscle cells responsible for regulating the entry of calcium into heart muscle cells. It plays a role in maintaining the heart beat and contraction. We have found that a lack of oxygen (hypoxia) alters the function of the L-type Ca2+ channel and its response to adrenergic stimulation (adrenaline).This may be one of the ways that rhythm disturbances or sudden cardiac death occurs with a heart attack. The activity of the L-type Ca2+ channel is sensitive to changes in reactive oxygen species caused by changes in oxygen concentration. The reactive oxygen species are generated from a part of the cell responsible for maintaining the cell's energy requirements (the mitochondria). Oxidative stress is a feature of various cardiovascular pathologies and we are now interested in determining the effect of oxidative stress on function of the L-type Ca2+ channel and the role of the mitochondria in generating reactive oxygen species. Oxidative stress can damage mitochondria leading to an increase in production of reactive oxygen species. We will determine how oxidative stress damages the mitochondria and how this then alters the channel function, directly or indirectly. The information gained will provide insight into how reactive oxygen species influence L-type Ca2+ channel function and the mechanisms that contribute to pathology involving reactive oxygen species such as heart failure and arrhythmia.

氧气对细胞的新陈代谢和功能至关重要。氧气输送到细胞是至关重要的，而心脏病发作期间发生的缺氧可能是致命的。L型Ca 2+通道是心肌细胞膜中的一种蛋白质，负责调节钙进入心肌细胞。它起着维持心脏跳动和收缩的作用。我们发现缺氧改变了L型钙通道的功能及其对肾上腺素能刺激的反应，这可能是心脏病发作时心律紊乱或心源性猝死的原因之一。L型Ca 2+通道的活性对氧浓度变化引起的活性氧变化敏感。活性氧是由负责维持细胞能量需求的细胞部分（线粒体）产生的。氧化应激是各种心血管疾病的一个特征，我们现在有兴趣确定氧化应激对L-型Ca 2+通道功能的影响以及线粒体在产生活性氧中的作用。氧化应激可损伤线粒体，导致活性氧产生增加。我们将确定氧化应激如何损害线粒体，以及这如何直接或间接地改变通道功能。所获得的信息将提供深入了解活性氧如何影响L型钙离子通道功能和机制，有助于病理涉及活性氧，如心力衰竭和心律失常。