Delcamp T J, Dales C, Ralenkotter L, Cole P S, Hadley R W
Department of Pharmacology, College of Medicine, University of Kentucky, Lexington, Kentucky 40536-0084, USA.
Am J Physiol. 1998 Aug;275(2):H484-94. doi: 10.1152/ajpheart.1998.275.2.H484.
The aim of this study was to investigate the role of mitochondrial ionic homeostasis in promoting reoxygenation-induced hypercontracture in cardiac muscle. Mitochondrial membrane potential and intramitochondrial Ca2+ concentration ([Ca2+]) were measured using confocal imaging in guinea pig ventricular myocytes exposed to anoxia and reoxygenation. Anoxia produced a variable, but often profound, mitochondrial depolarization. Some cells mounted a recovery of their mitochondrial membrane potential during reoxygenation; the depolarization was sustained in other cells. Recovery of the mitochondrial membrane potential seemed essential to avoid reoxygenation-induced hypercontracture. Reoxygenation also caused a sizable elevation in intramitochondrial [Ca2+], the amplitude of which was correlated with the likelihood of a cell undergoing hypercontracture. A sustained Ca2+ load analogous to that seen during reoxygenation was imposed on cardiac mitochondria through permeabilization of the plasma membrane. Elevation of intracellular [Ca2+] to 800 nM caused a substantial mitochondrial depolarization. We propose that the conditions seen in guinea pig ventricular myocytes during reoxygenation are well suited to produce Ca2+-dependent mitochondrial depolarization, which may play a significant role in promoting irreversible cell injury.
本研究的目的是探讨线粒体离子稳态在促进心肌复氧诱导的超收缩中的作用。在暴露于缺氧和复氧的豚鼠心室肌细胞中，使用共聚焦成像测量线粒体膜电位和线粒体内Ca2+浓度（[Ca2+]）。缺氧导致线粒体去极化程度不一，但通常较为显著。一些细胞在复氧过程中线粒体膜电位恢复；而在其他细胞中去极化持续存在。线粒体膜电位的恢复似乎对于避免复氧诱导的超收缩至关重要。复氧还导致线粒体内[Ca2+]显著升高，其幅度与细胞发生超收缩的可能性相关。通过质膜通透化，将类似于复氧期间所见的持续Ca2+负荷施加于心脏线粒体。将细胞内[Ca2+]升高至800 nM会导致线粒体大量去极化。我们认为，豚鼠心室肌细胞在复氧期间所见的情况非常适合产生Ca2+依赖性线粒体去极化，这可能在促进不可逆细胞损伤中起重要作用。
