Viola Helena M, Hool Livia C
School of Anatomy, Physiology and Human Biology, The University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia.
School of Anatomy, Physiology and Human Biology, The University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia.
Heart Lung Circ. 2014 Jul;23(7):602-9. doi: 10.1016/j.hlc.2014.02.009. Epub 2014 Feb 28.
Maintenance of cellular calcium homeostasis is critical to regulating mitochondrial ATP production and cardiac contraction. The ion channel known as the L-type calcium channel is the main route for calcium entry into cardiac myocytes. The channel associates with cytoskeletal proteins that assist with the communication of signals from the plasma membrane to intracellular organelles, including mitochondria. This article explores the roles of calcium and the cytoskeleton in regulation of mitochondrial function in response to alterations in L-type calcium channel activity. Direct activation of the L-type calcium channel results in an increase in intracellular calcium and increased mitochondrial calcium uptake. As a result, mitochondrial NADH production, oxygen consumption and reactive oxygen species production increase. In addition the L-type calcium channel is able to regulate mitochondrial membrane potential via cytoskeletal proteins when conformational changes in the channel occur during activation and inactivation. Since the L-type calcium channel is the initiator of contraction, a functional coupling between the channel and mitochondria via the cytoskeleton may represent a synchronised process by which mitochondrial function is regulated in addition to calcium influx to meet myocardial energy demand on a beat to beat basis.
维持细胞钙稳态对于调节线粒体ATP生成和心脏收缩至关重要。被称为L型钙通道的离子通道是钙进入心肌细胞的主要途径。该通道与细胞骨架蛋白相关联，这些蛋白有助于将信号从质膜传递到包括线粒体在内的细胞内细胞器。本文探讨了钙和细胞骨架在响应L型钙通道活性改变时对线粒体功能调节中的作用。L型钙通道的直接激活导致细胞内钙增加以及线粒体钙摄取增加。结果，线粒体NADH生成、氧消耗和活性氧生成增加。此外，当通道在激活和失活过程中发生构象变化时，L型钙通道能够通过细胞骨架蛋白调节线粒体膜电位。由于L型钙通道是收缩的启动者，通道与线粒体之间通过细胞骨架的功能偶联可能代表了一个同步过程，通过该过程除了钙内流之外还能调节线粒体功能，以逐搏满足心肌能量需求。
