Abstract
Mitochondria play a fundamental role in the energetics of cardiac cells. Moreover, mitochondria are involved in cardiac ischemia/reperfusion injury by opening the mitochondrial permeability transition pore which is the major cause of cell death. The preservation of mitochondrial function is an essential component of the cardioprotective mechanism. The involvement of mitochondrial K+ transport in this complex phenomenon seems to be well established. Several mitochondrial K+ channels in the inner mitochondrial membrane, such as ATP-sensitive, voltage-regulated, calcium-activated and Na+-activated channels, have been discovered. This obliges us to ask the following question: why is the simple potassium ion influx process carried out by several different mitochondrial potassium channels? In this review, we summarize the current knowledge of both the properties of mitochondrial potassium channels in cardiac mitochondria and the current understanding of their multidimensional functional role. We also critically summarize the pharmacological modulation of these proteins within the context of cardiac ischemia/reperfusion injury and cardioprotection.
Highlights
During ischemia/reperfusion injury, mitochondrial dysfunction is one of the initial triggers of cardiac death
Many studies have shown that the pharmacological activation of mitoKATP by potassium channel openers, such as diazoxide, pinacidil and BMS-191095, protects cardiac tissue and reduces the size of infarct after ischemia/reperfusion injury [7,9,52,56,60,69]
The first channel belonging to this group was the large-conductance calcium-activated potassium channel, which was found in mitochondria of mammalian heart tissue and in cardiac-derived cell lines [11,38,92,93,94,95]
Summary
During ischemia/reperfusion injury, mitochondrial dysfunction is one of the initial triggers of cardiac death This complex process involves a variety of events, such as changes in reactive oxygen species (ROS) synthesis, calcium ion overload in the mitochondria, disruption of mitochondrial membranes and a lack of ATP synthesis [1,2,3]. During ischemia, anaerobic glycolysis, ATP hydrolysis, and release of protons from acidic organelles cause the pH in cardiac tissues to decrease by one unit or more (≥10-fold increase of hydrogen ion concentration) [26,27,28] These factors (ATP, Ca2+, ROS/redox and pH) regulate the activity of mitochondrial potassium channels. We present examples and briefly explain the possible mechanisms of cardioprotection that are mediated by the activation of cardiac mitoK channels
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