Age-Dependent Brain Tissue Hydration, Ca Exchange and their Dose- Dependent Ouabain Sensitivity

Primary mechanism responsible for age-dependent neuronal dehydration

“…This suggestion is supported by the data that the curves of dose-dependent ouabain effect on 45 Ca 2+ efflux both in young and old animals had opposite character at ouabain concentrations of <10 -8 M (a 3 receptors), while they had parallel character at high concentrations (>10 -8 M). These data are in harmony with literature [63] and our previous data that a 3 receptors have more pronounced age-dependent character than a 2 and a 1 because of its high affinity to [Ca 2+ ] i [30]. The non-monotonic curve of ouabain dose-dependent effect on 45 Ca 2+ efflux in the study of brain tissue hydration of young rats (Fig.…”

“…After such procedure the full absence of somatic reflexes on extra stimuli was recorded. Based on our previous data [30] where the age-dependent kinetics of ouabain binding with α 3 receptors in brain cortex tissue is more pronounced than in subcortex and cerebellum tissues (in adult animals) the investigation of brain cortex tissue has been the subject of the present study. In vivo experiments, 30 min before decapitation animals were intraperitoneally injected with investigated solutions.…”

“…However, it is not clear the depression of which function (membrane iontransporting or cytoplasm signaling system) of pump is a primary mechanism for age-induced neuronal dehydration. Our previous study has shown that among three ouabain receptors (Na + /K + -ATPase), having low (α 1 ), middle (α 2 ) and high (α 3 ) affinities, α 3 isoform-dependent signaling system controlling cell hydration serves as an extra-sensitive and universal sensor for different chemical and physical signals [28], [29] and has pronounced age-dependent character [30], [31]. Therefore, we hypothesize that the dysfunction of Na + /K + -ATPase α 3 isoformdependent signaling system could serve as a primary mechanism for generation of age-dependent neuronal dehydration [28].…”

The net water uptake by excitable cells is a primary mechanism for pain signal generation

“…as synaptical transmitters, their agonists and antagonists as well as for ionizing and non-ionizing radiation [20][21][22][23][24][25]. Meanwhile, cGMPdependent F Na + /Ca 2+ exchange is more sensitive to aging and different factors than cAMP-dependent R Na + /Ca 2+ exchange [26][27][28]. It has been shown that the increase of lipid fluidity (~40%) by the involvement of non-metabolized decanoic fatty acid in neuronal membrane leads to cell swelling, which is accompanied by the increase of intracellular cGMP contents without changing intracellular cAMP level [3,29,30].…”

“…The study of the feedback effect of cGMP-dependent Na + /Ca 2+ exchange on cell hydration has shown that though Na + /Ca 2+ exchange functions in stoichiometry of 3Na + :1Ca 2+ , the F Na + /Ca 2+ exchange has dehydration effect on brain tissue in young (healthy) animals, while in older (nonhealthy) animals it has hydration effect. More detailed investigation of the nature of F Na +/ Ca 2+ exchange on brain tissue dehydration has shown that in healthy animals the cGMP-dependent F Na + /Ca 2+induced cell dehydration is due to activation of Na + /K + pump in result of [Ca 2+ ] i decrease [15,18,27]. Thus, F Na + /Ca 2+ exchange activation has pain-relieving effect as on one hand it leads to inhibition of membrane excitability by activation of Na + /K + pump through generation of water efflux from the cells and by membrane hyperpolarization, on the other hand it depresses synaptical signal transmission by decreasing [Ca 2+ ] i [6,[31][32][33].…”