Babskij A. Functional state of tissues and changes in Na+ ions under conditions of pathological hypoxia and cancerogenesis

Analysis of the energetic sources for Na+ transmembrane gradient in cardio-myocytes of healthy and diabetic hearts has been provided. It has been shown that glycolitic and Na+/K+-ATPase dysfunctions in diabetic cardiomyocytes were related to the increase in intracellular Na+ (Na+i). The lower ATP and phophocreatine and higher Na+i suggest that diabetic cardiomyocytes have depressed energetic function. It has been established that the typical for diabetic cardiomyocytes increase in Na+i leads to a disorder in both oxidative processes and ATP synthesis in mitochondria (MCh). While addition of Na+ (3 - 10 mM) decreased State 3 respiration and rate of oxidative phosphorylation in both diabetic and control MCh, the decrease were sig-nificantly greater for diabetic than for control. The Na+ effect was reversed by pro-viding different levels of extramitochondrial Ca2+ (larger Ca2+ levels were needed to reverse the Na+ depressant effect in diabetes mellitus than in control) and be inhibit-ing the Na+/Ca2+ exchanger function. Thus, for the first time it has been shown that the increase in Na+i induces depletion of intramitochondrial Ca2+ due to activation of Na+/Ca2+ exchanger in mitochondrial membrane. The 31P nuclear magnetic reso-nance (MR) spectroscopy data support our hypothesis that in diabetic cardiomyo-cytes, increased Na+ leads to decrese in ATP level, and that changes are related to Na+ induced depletion of intramitochondrial Ca2+.