Aging Leads to Over-Expression of Na⁺/K⁺Pump Units in Liver and Na⁺/Ca²⁺Exchangers in Brain Cortex

The metabolic controlling of tissue hydration is the fundamental parameter determining cell functional activity and its dysfunction is the common consequence of any cell pathology, including aging. The aim of the present study is to reveal the differences of age-dependent metabolic controlling of cell hydration of excitable tissue such as brain cortex and non-excitable tissues such as liver and spleen. For this purpose, the age-dependent sensitivity of cell hydration in excitable and non-excitablet issues is studied through depressing metabolic activity by cooling and its activation by supplying animals with distilled water, by inactivation of Na+/K+ pump and activation of Na+/Ca2+ exchange in the reverse mode. The obtained data bring us to the conclusion that the metabolic regulation of cell hydration in excitable tissue is realized by the activation of electrogenic Na+/K+ pump and Na+/Ca2+ exchange in the cell membrane and the formation of endogen water by mitochondrial activity, while the regulation of cell hydration in non-excitable tissue is carried out only by the activity of mitochondrial function. Aging leads to an over-expression of Na+/K+ pump units in liver and Na+/Ca2+ exchanger in brain cortex of rats.

Age-Dependent Comparative Study of 4 Hz and 8 Hz EMF Exposure on Heart Muscle Tissue Hydration of Rats

Previously we have shown that 4 Hz and 8 Hz EMF exposures have depressing effect on the thermodynamic activity of water, which decreases peroxide formation. It has also been shown that 4 Hz EMF-treated physiological solution modulates the growth and development of microbes and heart muscle contractility, but 8 Hz EMF has pronounced inhibitory effect on bacterial growth and development. Therefore, in order to elucidate the possible mechanism of 4 Hz and 8 Hz EMF effects on heart muscle function, in the present work the effects of 4 Hz and 8 Hz EMF exposures on heart muscle tissue hydration, the sensitivity of 4 Hz and 8 Hz EMF-induced tissue hydration to 10−4 M ouabain (Na+/K+ pump inhibition) and 10−9 M ouabain (activation of intracellular signaling system) as well as the effects of 4 Hz and 8 Hz EMF exposures on the number of Na+/K+ pump units in the membrane of both young and old rats have been studied. The obtained data allow us to suggest that 8 Hz EMF exposure has more pronounced age-dependent modulation effect on tissue hydration of heart muscle than 4 Hz EMF and this effect is sensitive to Na+/K+ pump activity and intracellular signaling system.

The Radioactive ⁴⁵Ca Cannot Be Used for Adequate Estimation of the Functional Activity of ⁴⁰Ca Ions in Cells and Organisms

Previously we have shown that nM ouabain-induced activation of cAMP-dependent Na/Ca exchange in reverse (R) mode in cell membrane has age-dependent weakening hydration effect on heart muscle and brain tissues and such Na/Ca exchange is characterized by quantum mechanical sensitivity. As in biological experiments radioactive 45Ca is used for the study of cold 40Ca exchange in cells and organisms, in the present work, the age-dependent effect of physiological solution (PS) containing either 40Ca or 45Ca on tissue hydration in different experimental conditions was studied in order to evaluate the bioequivalence of these two forms of Ca. The obtained data indicate that the intraperitoneal injections of 40Ca PS and 45Ca PS leading to activation of RNa/40Ca and RNa/45Ca exchanges, respectively, have different age-dependent effects on heart muscle and brain tissue hydration. As in myocyte membrane, the Na/Ca exchange is more expressed than in neuronal membrane, the age-dependent heart muscle hydration is more sensitive to quantum properties of Ca than brain tissue hydration. The [45Ca]i, in contrary to [40Ca]i, has age-dependent weakening and stabilizing effect on tissue hydration and makes the latter insensitive to ouabain. The obtained data bring us to a strong conclusion that RNa/Ca exchange has quantum mechanical properties and in biological experiments radioactive 45Ca cannot be used for adequate estimation of the functional activity of 40Ca ions in cells and organisms.

The Quantum-Mechanical Sensitivity of Cell Hydration in Mammals

The elucidation of the mechanism on the biological effects of weak chemical and physical factors on cells and organism is one of the modern problems in life sciences. According to the Receptor Theory of Prof. Bernard Katz the impact of the biological substances on cells is realized through the activation of ligand-gated ion channels in the membrane. However, this theory doesn’t provide a satisfactory explanation on the similar biological effects of extremely low concentrations of different chemical substances, which are unable to activate the ionic channels in the membrane and have non-linear dose-dependent effect on cells. Previously we have suggested that the metabolic control of cell hydration serves as a universal quantum-mechanical sensor for different weak physical and chemical signals. For supporting this hypothesis, in this article the comparative study of the effects of low concentrations of both cold (non-radioactive) and [3H]-ouabain (specific inhibitor for Na+/K+-ATPase) on the hydration in different tissues of rats has been performed. The obtained data have shown that cold and [3H]-ouabain have different effects on cell hydration and such a difference depends on the initial metabolic state of tissues. On the basis of our previous and present results it is suggested that such a quantum-mechanical sensitivity of cell hydration is realized through the cyclic-nucleotides-dependent Na+/Ca2+ exchange, having a crucial role in the metabolic regulation of cell hydration.

The Quantum-Mechanical Sensitive Na/K Pump Is a Key Mechanism for the Metabolic Control of Neuronal Membrane Function

At present, there are relevant scientific materials on the cellular and molecular mechanisms of electrogenic Na/K pump function and structure, as well as on the potential- and ligand-activated ionic channels in the membrane. However, the role of electrogenic Na/K pump in regulation of semipermeable properties of cell membrane has not been elucidated yet, which is due to the fact that our knowledge about the biophysical properties of cell membrane is based on the conductive membrane theory of Hodgkin-Huxley-Katz, which is developed on internally perfused squid axon and lacks intracellular metabolism. Thus, the accumulated abundance of data on the role of G-proteins-dependent intracellular signaling system in regulation of Na/K pump activity and biophysical properties of cell membrane presumes fundamental revision of some statements of membrane theory. The aim of the present review is to briefly demonstrate our and literature data on cell hydration-induced auto-regulation of Na/K pump as well as on its role in metabolic control of semipermeable properties and excitability of neuronal membrane, which are omitted in the study of internally perfused squid axon.