How does oxygen regulate Ca2+ channel function in cardiac myocytes?
How does oxygen regulate Ca2+ channel function in cardiac myocytes?
批准号:
nhmrc : 254504
负责人:
A/Pr Livia Hool
金额:
$31.71万
依托单位国家:
澳大利亚
项目类别:
NHMRC Project Grants
财政年份:
2003
资助国家:
澳大利亚
项目状态:
已结题
起止时间:
2003-01-01 至 2005-12-31
中文摘要
氧在细胞的新陈代谢和功能中起着关键作用。向细胞输送氧气是至关重要的,心脏病发作期间发生的缺氧可能是致命的。死亡通常是由心律失常或心跳紊乱引起的。异常的心跳不能使心脏有效地泵血,从而剥夺了重要的器官。确切地说,心律失常是如何引起的还不清楚。正常的心跳是电信号通过心肌细胞传播的结果。这种电活动是由盐或离子通过称为离子通道的膜蛋白运动而产生和维持的。其中,L型钙通道在心脏的兴奋和收缩中起着至关重要的作用。氧的减少改变了L型钙通道的功能。然而,这一点的确切机制尚不确定。细胞中的氧感应机制负责低氧时通道功能的调节。氧气传感器的确切身份目前是争论的中心。提出了四个假设。这项提案旨在详细检查氧气传感的四个假设,以确定氧气传感器的身份。这些信息应该会增加我们对钙通道在应激条件下如何发挥作用的理解,例如在心脏病发作期间。
英文摘要
Oxygen occupies a key role in cellular metabolism and function. Oxygen delivery to cells is critical and lack of oxygen such as occurs during a heart attack can be lethal. Death occurs commonly by induction of arrhythmia or a disturbance in the heart beat. The abnormal heart beat cannot enable the heart to pump blood efficiently and vital organs are then deprived.Exactly how arrhythmia is induced is not understood. The normal heart beat occurs as a result of propogation of electrical signals through heart muscle cells. The electrical activity is generated and sustained by movement of salts or ions through membrane proteins known as ion channels. One of these channels, the L-type calcium channel plays a vital role in cardiac excitation and contraction. A reduction in oxygen alters the function of the L-type calcium channel. However, the exact mechanism for this is uncertain. An oxygen sensing mechanism in the cell is responsible for the regulation of channel function during hypoxia. The exact identity of the oxygen sensor is currently the centre of debate. Four hypotheses have been proposed. This proposal aims to examine in detail the four hypotheses of oxygen sensing to definitively determine the identity of the oxygen sensor. This information should increase our understanding of how calcium channels function during stressful conditions such as during a heart attack.
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