Vol 14, No 1 (2016)

This review is devoted to analysis of current research about the role of mitochondrial ATP-dependent potassium channel (mitoКАТP) in the regulation of metabolic processes of the cell. The mechanisms of cell adaptation to hypoxia and ischemia involving mitoКАТP is considered in the article. The opportunity of pharmacological modulation of mitoКАТP activity to stimulate processes of cell adaptation to damaging factors is discussed. This approach seems promising for the development of effective pharmacotherapy of diseases which have in their pathogenesis the state of hypoxia and ischemia.

The purpose of the paper was experimental study of activity of energy production of the heart, liver and kidney after harmful action of general vibration with 8 and 44 Hz frequency. The functional state of native mitochondria in tissue homogenates was studied by polarographic method by means of closed oxygen device of halvanic type in thermostated cuvette of 1 ml volume in the salt medium of incubation. Metabolic states of mitochondria of the rabbit heart, liver and kidney were modeled in vitro in oxidation of endogenous substrates (before and after administration of inhibitors of different stages of breath chain) varying exogenous substrates (before and after administration of 2.4-DNP into the cell). In order to synchronize the changes in short time, the incomplete cycle of metabolic states “endogenous breath → rest → activity” was used. The velocity of mitochondrial oxidation of endogenous substrates was determined by tissue type, and was 16.3 ± 4.3, 5.2 ± 0.6 and 8.13 ± 1.4 ng-atom О min-1mg-1 protein for the heart, liver and kidney of intact animals respectively. In the heart, after high frequent vibration, the reduction of oxidation velocity of NAD-dependent substrates in rest and in active metabolic state of mitochondria was 43 % (р ≤ 0.05) and 30 % (р ≤ 0.01) respectively, while the velocity of oxidation for endogenous succinic acid increased by 77 % (р ≤ 0.05) to 21st session of vibration, then constantly decreasing to the end of vibration sessions. The same changes but in less degree were registerted in the liver and kidney. The systems of energy production of the heart and the studied parenchimatic organs were involved in reaction on vibration exposure and reacted typically by low energetic shift with hyperactivation of endogenous succinic acid system of oxidation and inhibition of NAD-depended part of the breath chain of mitochondria. Therefore, the study of bioenergetics mechanisms of hypoxia in different tissues allows to clear the molecular targets for pharmacological action by means of substrate antihypoxants.

The review of literature is devoted to researches in vitro and in vivo in which functioning changes P-glycoprotein (Pgp) under the influence of hypoxia of different types are shown. In the majority of scientific works activation of expression and functional activity of Pgp is shown that authors connect with activation of HIF-1 and Sp1 which are described in more detail. However a number of researches disproves the conclusion about induction of activity of Pgp in the conditions of hypoxia that testifies about difficult mechanisms involved in regulation of Pgp activity, their dependence on a type and duration of hypoxia, redox status and other parameters.