Primary mechanism responsible for age-dependent neuronal dehydration
Keywords:Brain Cortex, 45Ca2 Efflux, 45Ca2 Uptake, Na /K -ATPase A3 Isoform, Tissue Hydration.
Neuronal dehydration and high [Ca2+]i are essential hallmarks for age-dependent memory impairment. Na+/K+-ATPase, having membrane transporting and intracellular signaling functions, has age-induced dysfunctional character. Therefore, it could have a key role in age-dependent neuronal dehydration and increase of [Ca2+]i. However, it is not clear the dysfunction of which above mentioned functions of Na+/K+-ATPase serves as a primary mechanism for generation of age-dependent neuronal dehydration and increase of [Ca2+]i. In present work age-dependent effects of â‰¤10-9M (agonist for Î±3 isoform which has only signaling function) and 10-4M ouabain (agonist for Î±1 isoform which has ion-transporting function) on brain cortex tissue hydration, 45Ca2+ uptake and 45Ca2+ efflux through plasma membrane were studied. It was shown that â‰¤10-9M and 10-4M ouabain concentrations have stimulation effects on cortex tissue hydration and Na+/Ca2+ exchange in reverse mode. However, these effects have age-dependent weakening and increasing characters, respectively. It is suggested that â‰¤10-9M ouabain-induced tissue hydration is due to cAMP-activated Ca2+-ATPase in endoplasmic reticulum membrane leading to reversion of Na+/Ca2+ exchange and elevation of endogenous H2O release in cytoplasm. This effect has age-dependent depressing character. Thus, the dysfunction of Î±3 isoform-dependent intracellular signaling system could be considered as a primary mechanism for age-dependent neuronal dehydration.
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