Functioning of the mitochondrial ATP-dependent potassium channel in rats varying in their resistance to hypoxia. Involvement of the channel in the process of animal’s adaptation to hypoxia
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The mechanism of tissue protection from ischemic damage by activation of the mitochondrial ATP-dependent K+ channel (mitoKATP) remains unexplored. In this work, we have measured, using various approaches, the ATP-dependent mitochondrial K+ transport in rats that differed in their resistance to hypoxia. The transport was found to be faster in the hypoxia-resistant rats as compared to that in the hypoxia-sensitive animals. Adaptation of animals to the intermittent normobaric hypoxia increased the rate of transport. At the same time, the intramitochondrial concentration of K+ in the hypoxia-sensitive rats was higher than that in the resistant and adapted animals. This indicates that adaptation to hypoxia stimulates not only the influx of potassium into mitochondria, but also K+/H+ exchange. When mitoKATP was blocked, the rate of the mitochondrial H2O2 production was found to be significantly higher in the hypoxia-resistant rats than that in the hypoxia-sensitive animals. The natural flavonoid-containing adaptogen Extralife, which has an evident antihypoxic effect, increased the rate of the mitochondrial ATP-dependent K+ transport in vitro and increased the in vivo tolerance of hypoxia-sensitive rats to acute hypoxia 5-fold. The involvement of the mitochondrial K+ transport in the mechanism of cell adaptation to hypoxia is discussed.
KeywordsMitochondrial ATP-dependent K+ channel K+/H+ exchange ROS Hypoxia Adaptation Flavonoid-containing adaptogen
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