ABSTRACT
Homology of the amino acid sequence of the mitochondrial potassium-transporting protein (MW 57kDa), having the properties of a channel subunit of the mitochondrial ATP-dependent potassium channel, and calreticulin (MW 55kDa) was detected by MALDI-TOF-TOF analysis method. Inhibitory analysis of ATP-dependent potassium transport in mitochondria with polyclonal antibodies to calreticulin was carried out. A dose-dependent inhibition of potassium transport in mitochondria by these antibodies was shown. The maximum value of inhibition was 55-60%. Based on these data it is hypothesized that at least two types of ATP-sensitive potassium channels are localized in mitochdndrial membrane. It is expected that the type of mitochondrial ATP-dependent potassium channel, which includes homologous calreticulin protein is localized mainly at mitochondrial and reticulum membrane contact sites.
Subject(s)
Adenosine Triphosphatases/metabolism , Calbindin 2/metabolism , Cation Transport Proteins/metabolism , Mitochondria, Liver/metabolism , Mitochondrial Membranes/metabolism , Mitochondrial Proteins/metabolism , Animals , Antibodies/pharmacology , Calbindin 2/antagonists & inhibitors , Male , Mitochondrial Proteins/antagonists & inhibitors , Rats , Rats, Wistar , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
Activity of mitochondrial ATP-dependent potassium channel in rats with high genetically determined resistance to hypoxia was higher than in sensitive animals. Adaptation of low resistant rats to hypoxia was accompanied by activation of the channel, facilitation of potassium recycling in mitochondria, and a decrease in the rate of H2O2 formation. Our results indicate that mitochondrial ATP-dependent potassium channel plays an important role in the delayed mechanisms of animal's adaptation to hypoxia.
Subject(s)
Acclimatization/physiology , Hypoxia/metabolism , KATP Channels/metabolism , Potassium/metabolism , Adenosine Triphosphate/metabolism , Adenosine Triphosphate/pharmacology , Animals , Disease Resistance , Hydrogen Peroxide/metabolism , Hypoxia/genetics , Hypoxia/physiopathology , KATP Channels/agonists , Male , Mitochondria, Heart/drug effects , Mitochondria, Heart/metabolism , Mitochondria, Liver/drug effects , Mitochondria, Liver/metabolism , RatsABSTRACT
Changes in the rate of respiration and functioning of the ATP-dependent potassium channel the liver and heart mitochondria of one-, three-, eight-, and twenty four-month-old Wistar male rats have been investigated. It was shown that the activity of the channel in the mitochondria of both tissues in 24-months-old animals decreases more than three times, and the content of potassium, 1.5-2 times compared with young one-month-old rats. The changes occur against the background of age-related decrease of energy supply in mitochondria, the respiratory complex-I underganig the greatest changes upon aging. The decrease of channel activity may be the result of changes in channel sensitivity to modulators and a decrease in the expression of mitochondrial K(+)-transporting channel-protein with a molecular mass of 5.5 kDa upon aging found in this work. As a result, the functioning of not only the mitoK(ATP) but also the whole mitochondrial potassium cycle is impaired.
Subject(s)
Aging/metabolism , KATP Channels/physiology , Mitochondria, Heart/metabolism , Mitochondria, Liver/metabolism , Adenosine Triphosphate/biosynthesis , Animals , Biological Transport , Electron Transport Complex I/metabolism , Energy Metabolism , Male , Phosphorylation , Potassium/metabolism , RatsABSTRACT
Flavonoid-containing plant preparations (water soluble extracts of Pentaphylloides fruticosa [Extralife], Emblica officinalis Gaerth [Amla], and Bergenia crassifolia [Bergenia]) produced a dose-dependent and tissue-specific effect on activity of mitochondrial ATP-dependent potassium channel. The effect of these preparations was biphasic (activation and inhibition). The activating effect of Extralife was one order of magnitude higher than that of Amla and Bergenia and was observed in a wider concentration range. The activating effect of preparations was abolished by inhibitors of the mitochondrial ATP-dependent potassium channel, which attested to specificity of their influence on mitochondrial channel. Under in vivo conditions, the antihypoxic effect of Extralife was partially abolished by mitochondrial ATP-dependent potassium channel inhibitor 5-hydroxydecanoate.
