Primary mechanism responsible for age-dependent neuronal dehydration

  • Authors

    • Anna Nikoghosyan Life Sciences International Postgraduate Educational Center, UNESCO Chair Armenia, Yerevan
    • Armenuhi Heqimyan Life Sciences International Postgraduate Educational Center, UNESCO Chair Armenia, Yerevan
    • Sinerik N. Ayrapetyan Life Sciences International Postgraduate Educational Center, UNESCO Chair Armenia, Yerevan
    2015-12-09
    https://doi.org/10.14419/ijbas.v5i1.5388
  • Brain Cortex, 45Ca2 Efflux, 45Ca2 Uptake, Na /K -ATPase A3 Isoform, Tissue Hydration.

  • Abstract

    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 ≤10-9M (agonist for α3 isoform which has only signaling function) and 10-4M ouabain (agonist for α1 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 ≤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 ≤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 α3 isoform-dependent intracellular signaling system could be considered as a primary mechanism for age-dependent neuronal dehydration.

  • References

    1. [1] G. Casadesus, P.I. Moreira, A. Nunomura, et al, Indices of metabolic dysfunction and oxidative stress, Neurochem Res, 32 (2007) 717-722. http://dx.doi.org/10.1007/s11064-007-9296-y.

      [2] D. Evans, Osmotic and ionic regulation: cells and animals, CRC Press: New York, 2009; 590.

      [3] E.K. Hoffmann, N.B. Holm, I.H. Lambert, Functions of volume-sensitive and calcium-activated chloride channels, IUBMB Life, 66 (2014) 257-67. http://dx.doi.org/10.1002/iub.1266.

      [4] L. Minkoff, HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed? Term=Minkoff%20L%5BAuthor%5D&cauthor=true&cauthor_uid=R. Damadian, Biological ion exchange resins, X. The Cytotonus hypothesis: Biological contractility and the total regulation of cellular physiology through quantitative control of cell water, Physiol Chem Phys, 8 (1976) 349-87.

      [5] G.M. Toney, Regulation of neuronal cell volume: from activation to inhibition to degeneration, J Physiol, 588 (2010) 3347–3348. http://dx.doi.org/10.1113/jphysiol.2010.197251.

      [6] S.N. Ayrapetyan, on the physiological significance of the pump-induced cell volume changes, Advances in Physiological Science, neurobiology of Invertebrates, J. Salanki, 1980; 67-82.

      [7] S.N. Ayrapetyan, V.L. Arvanov, on the mechanism of the electrogenic sodium pump dependence of membrane chemosensitivity, Comp Biochem Physiol, 64 (1979) 601-604. http://dx.doi.org/10.1016/0300-9629(79)90592-9.

      [8] S.N. Ayrapetyan, M.A. Suleymanyan, A.A. Sagian, S.S. Dadalyan, Autoregulation of electrogenic sodium pump, Cel Mol Neurobiol, 4 (1984) 367–384.

      [9] S.N. Ayrapetyan, G.Y. Rychkov, M.A. Suleymanyan, Effects of water flow on transmembrane ionic currents in neurons of Helix pomatia and in Squid giant axon, Comp Biochem Physiol, 89 (1988) 179-186. http://dx.doi.org/10.1016/0300-9629(88)91076-6.

      [10] R.G. Parton, K. Simons, The multiple faces of caveolae, Nat Rev Mol Cell Bio, 8 (2007) 185-194. doi: 10.1038/nrm2122. http://dx.doi.org/10.1038/nrm2122.

      [11] V.A. Parsegian, R.P. Rand, D.C. Rau, Osmotic stress, crowding, preferential hydration and binding: a comparison of perspectives, Proc Natl Acad Sci USA, 97 (2000) 3987-3992. http://dx.doi.org/10.1073/pnas.97.8.3987.

      [12] S. Ayrapetyan, M. Suleymanyan, H. Gevorgyan, G. Arakelov, The swelling as a protective reaction of cell, Reports Acad Sci USSR, 255 (1980) 111-115. (in Russian).

      [13] D. Haussinger, The role of cellular hydration in the regulation of cell function, Biochem J, 313 (1996) 697-710. http://dx.doi.org/10.1042/bj3130697.

      [14] G.I. McIntyre, Cell hydration as the primary factor in carcinogenesis: a unifying concept, Med Hypotheses, 66 (2006) 518-26. http://dx.doi.org/10.1016/j.mehy.2005.09.022.

      [15] M. Secher, P. Ritz, Hydration and cognitive performance, J Nutr Health Aging, 16 (2012) 325-329. http://dx.doi.org/10.1007/s12603-012-0033-0.

      [16] H. Huang, F.I. Lu, S. Jia, et al, Amotl2 is essential for cell movements in zebrafish embryo and regulates c-Src translocation, Development, 134 (2007) 979-988. http://dx.doi.org/10.1242/dev.02782.

      [17] K.R. Cooke, Ouabain and regulation of cellular volume in freshly prepared slices of rabbit renal cortex, J Physiol, 279 (1978) 361-374. http://dx.doi.org/10.1113/jphysiol.1978.sp012349.

      [18] S. Ayrapetyan, M. Sulejmanyan, on the pump-induced cell volume changes, Comp Biochem Physiol, 64 (1979) 571–575. http://dx.doi.org/10.1016/0300-9629(79)90585-1.

      [19] D. Carpenter, M. Fejtl, S. Ayrapetyan, D. Szarowski, J. Turner, Dynamic changes in neuronal volume resulting from osmotic and sodium transport manipulations, Acta Biol Hung, 43 (1992) 39-48.

      [20] S.N. Ayrapetyan, Na-K pump and Na:Ca exchanger as metabolic regulators and sensors for extraweak signals in neuromembrane, Modern problems of cellular and molecular biophysics, S.N. Ayrapetyan, A.C.T. North , Yerevan: Noyan Tapan, 2001; 31-57.

      [21] F. Lang, Mechanisms and significance of cell volume regulation, J Am Coll Nutr, 26 (2007) 613S-623S. http://dx.doi.org/10.1080/07315724.2007.10719667.

      [22] P. Hoffmann, T.J. Boeld, R. Eder, Loss of FOXP3 expression in natural human CD4+CD25+ regulatory T cells upon repetitive in vitro stimulation, Eur J Immunol, 39 (2009) 1088-1097. http://dx.doi.org/10.1002/eji.200838904.

      [23] S.N. Ayrapetyan, Metabolically dependent fraction of membrane potential and electrode properties of the membrane of giant neurons in mollusks, Neuroscience Translations, 4 (1970) 53-57. http://dx.doi.org/10.1007/BF01126316.

      [24] R.C. Thomas, Electrogenic sodium pump in nerve and muscle cells, Physiol Rev, 52 (1972) 563-594.

      [25] F. Lang, E.K. Hoffmann, Cell role of ion transport in control of apoptotic cell death, Compr Physiol, 2 (2012) 2037-2061. http://dx.doi.org/10.1002/cphy.c110046.

      [26] A.L. Lehninger, Mitochondria and calcium ion transport, Biochem J, 119 (1970) 129–138. http://dx.doi.org/10.1042/bj1190129.

      [27] A.L. Hodgkin, The conduction of the nervous impulse, Liverpool, UK, Liverpool University Press, 1964.

      [28] S.N. Ayrapetyan, Cell hydration variation is a primary mechanism for intracellular signaling system, J Bioequiv Availab, 5 (2013) 136-141. http://dx.doi.org/10.4172/jbb.10000e35.

      [29] S. Ayrapetyan, N. Baghdasaryan, Y. Mikayelyan, et al, Cell hydration as a marker for nonionizing radiation, Electromagnetic Fields in Biology and Medicine, M. Markov, USA: CRC Press, 2015; 193-215. http://dx.doi.org/10.1201/b18148-14.

      [30] S. Ayrapetyan, A. Heqimyan, A. Nikoghosyan, Age-dependent brain tissue hydration, Ca exchange and their dose-dependent ouabain sensitivity, J Bioequiv Availab, 4 (2012 060-068. doi.org/10.4172/jbb.1000114.

      [31] A. Heqimyan, L. Narinyan, A. Nikoghosyan, S. Ayrapetyan, Age-dependent magnetic sensitivity of brain and heart muscles, Electromagnetic Fields in Biology and Medicine, M. Markov , USA: CRC Press, 2015; 217-230. http://dx.doi.org/10.1201/b18148-15.

      [32] R.A. Haworth, A.B. Goknur, H.A. Bertroff, Inhibition of Na-Ca exchange by general anesthetics, Circ Res, 65 (1989) 1021-1028. http://dx.doi.org/10.1161/01.RES.65.4.1021.

      [33] K. Krnjevic, Cellular and synaptic actions of general anaesthetics, Gen Pharmacol, 23 (1992) 965-975. http://dx.doi.org/10.1016/0306-3623(92)90274-N.

      [34] A. Heqimyan, A. Deghoyan, S. Ayrapetyan, Ketamine – induced cell dehydration as a mechanism of its analgesic and anesthetic effects, J Int Dent Med Res, 4 (2011) 42-49.

      [35] R. Dipolo, L. Beauge, Sodium/calcium exchanger: influence of metabolic regulation on ion carrier interactions, Physiol Rev, 86 (2006) 155-203. http://dx.doi.org/10.1152/physrev.00018.2005.

      [36] R. Takahashi, M. Aprison, Acetylcholine content of discrete areas of the brain obtained by a near-freezing method, J Neurochem, 11 (1964) 887-898. http://dx.doi.org/10.1111/j.1471-4159.1964.tb06740.x.

      [37] R.H. Adrian, The effect of internal and external potassium concentration on the membrane potential of frog muscle, J Physiol, 133 (1956) 631–658. http://dx.doi.org/10.1113/jphysiol.1956.sp005615.

      [38] A.S. Keston, R. Brandt, The fluorometric analysis of ultramicro quantities of hydrogen peroxide, Anal BiocheHYPERLINK "http://www.sciencedirect.com/science/journal/00032697", 11 (1965) 1-5. http://dx.doi.org/10.1016/0003-2697(65)90034-5.

      [39] Z.S. Khachaturian, The role of calcium regulation in brain aging: reexamination of a hypothesis, Aging (Milano), 1 (1989) 17-34. http://dx.doi.org/10.1007/bf03323872.

      [40] P. Kostyuk, E. Lukyanetz, Intracellular calcium signaling-basic mechanisms and possible alterations, Bioelectromagnetics: Current Concepts. NATO Science Series, S. Ayrapetyan, M. Markov, Dordrecht (Netherland): Springer Press, 2006; 87-122.

      [41] M. Brini, E. Carafoli, Calcium pumps in health and disease, Physiol Rev, 89 (2009) 1341-1378. http://dx.doi.org/10.1152/physrev.00032.2008.

      [42] P.F. Baker, M.P. Blaustein, A.L. Hodgkin, S.A. Steinhardt, The influence of calcium on sodium efflux in squid axons, J Physiol, 200 (1969) 431-458. http://dx.doi.org/10.1113/jphysiol.1969.sp008702.

      [43] M.P. Blaustein, J. Zhang, L. Chen, H. Song, H. Raina, The pump, the exchanger, and endogenous ouabain: signaling mechanisms that link salt retention to hypertension, Hypertension, 53 (2009) 291-298. http://dx.doi.org/10.1161/HYPERTENSIONAHA.108.119974.

      [44] M. Juhaszova, M. Blaustein, Na+ pump low and high ouabain affinity alpha subunit isoforms are differently distributed in cells, Proc Natl Acad Sci USA, 94 (1997) 1800-1805. http://dx.doi.org/10.1073/pnas.94.5.1800.

      [45] M.P. Blaustein, W.J. Lederer, Sodium/calcium exchange: its physiological implications, Physiol Rev, 79 (1999) 763–854.

      [46] F.A. Fuhrman, H.H. Ussing, A characteristic response of the isolated frog skin potential to neurohypophysial principles and its relation to the transport of sodium and water, J Cell Physiol, 38 (1951) 109-130. http://dx.doi.org/10.1002/jcp.1030380109.

      [47] D.C. Tosteson, J.F. Hoffman, Regulation of cell volume by active cation transport in high and low potassium sheep red cells, J Gen Physiol, 44 (1960) 169-194. http://dx.doi.org/10.1085/jgp.44.1.169.

      [48] A.A. Mongin, S.N. Orlov, Mechanisms of cell volume regulation and possible nature of the cell volume sensor, Pathophysiology, 8 (2001) 77-88. http://dx.doi.org/10.1016/S0928-4680(01)00074-8.

      [49] A.S. Troshin, The membrane theory of cell permeability, Problems of Cell Permeability W.E. Widdas, Pergamon Press: Oxford, 1966; 5-27.

      [50] G.H. Pollack, Phase transitions and the molecular mechanism of contraction, Biophys Chem, 59 (1996) 315-328.

      [51] G.N. Ling, A convergence of experimental and theoretical breakthroughs affirms the PM theory of dynamically structured cell water on the theory’s 40th birthday, Water and the Cell, G. Pollack, Netherlands: Springer, 2006; 1-52.

      [52] S.N. Ayrapetyan, V.L. Arvanov, S.B. Maginyan, K.V. Azatyan, Further study of the correlation between Na-pump activity and membrane chemosensitivity, Cell Mol Neurobiol, 5 (1985) 231-43.

      [53] I.V. Chizmakov, Z.A. Sorokina, Temperature-independence of the effect of osmotic pressure on the inward sodium current in the membrane of isolated spinal ganglion neurons of the rat, Neurophysiologiia, 18 (1986) 518-525. (in Russian).

      [54] G. Rychkov, M.A. Suleymanyan, S.N. Ayrapetyan, Dependence of water flow effect on the ionic currents of dialyzed neuron of somatic membrane fluidity, Biol Membr, 6 (1989) 733-740. (in Russian).

      [55] A. Macknight, A. Leaf, Regulation of cellular volume, Physiol Rev, 57 (1977) 510-573.

      [56] J.C. Skou, The influence of some cations on an adenosine triphosphatase from peripheral nerves, Biochim Biophys Acta, 23 (1957) 394-401.

      [57] Z. Xie, A. Askari, Na+/K+-ÐТPase as a signal transducer, Eur J Biochem, 269 (2002) 2434-2439.

      [58] Z. Li, Z. Xie, The sodium pump and cardiotonic steroids-induced signal transduction protein kinases and calcium-signaling microdomain in regulation of transporter trafficking, Biochim Biophys Acta, 1802 (2010) 1238-1245.

      [59] K.J. Sweadner, Isozymes of the Na+/K+-ATPase, Biochim Biophys Acta, 988 (1989) 185-220.

      [60] I. Berrebi-Bertrand, J.M. Maixent, G. Christe, L.G. Lelievre, Two active Na+/K+-ATPases of high affinity for ouabain in adult rat brain membranes, Biochim Biophys Acta, 1021 (1990) 148-156.

      [61] K.M. McGrail, J.M. Phillips, K.J. Sweadner, Immunofluorescent localization of three Na+/K+-ATPase isozymes in the rat central nervous system: both neurons and glia canexpress more than one Na+/K+-ATPase, J Neurosci, 11 (1991) 381-391.

      [62] N. Cholet, L. Pellerin, P.J. Magistretti, E. Hamel, Similar perisynaptic glial localization for the Na+/K+-ATPase alpha 2 subunit and the glutamate transporters GLAST and GLT-1 in the rat somatosensory cortex, Cereb Cortex, 12 (2002) 515–25.

      [63] G.R. De Lores Amaiz, M.G. Ordieres, Brain Na (+), K (+)-ATPase activity in aging and disease, Int J Biomed Sci, 10 (2014) 85-102.

      [64] A.A. Saghian, S.N. Ayrapetyan, D.O. Carpenter, Low concentrations of cuabain stimulate Na:Ca exchange in neurons, Cell Mol Neurobiol, 16 (1996) 180-185.

      [65] S.N. Airapetyan, Effect of temperature on membrane potential of giant neurons in snails. Neuroscience Translations, 3 (1969) 5-9.

      [66] S.N. Ayrapetyan, The functional significance of electrogenic sodium pump in neurons, Problems of Brain Biochem, 9 (1974) 233-250. (in Russian).

      [67] M. Hirata, F. Murad, Interrelationships of cyclic GMP, inositol phosphates, and calcium, Adv Pharmacol, 26 (1994) 195-216.

      [68] K.V. Azatian, S.N. Ayrapetyan, D.O. Carpenter, Metabotropic GABA receptors regulate acetylcholine responses on snail neurons, Gen Pharmacol, 29 (1997) 67–72.

      [69] E.A. Nagelhus, O.P. Ottersen, Physiological roles of Aquaporin-4 in brain, Physiol Rev, 93 (2013) 1543-1562.

      [70] C. Giorgi, D. De Stefani, A. Bononi, R. Rizzuto, P. Pinton, Structural and functional link between the mitochondrial network and the endoplasmic reticulum, Int J Biochem Cell Biol, 41 (2009) 1817–1827.

      [71] P. Pinton, C. Giorgi, R. Siviero, E. Zecchini, R. Rizzuto, Calcium and apoptosis: ER- mitochondria Ca2+ transfer in the control of apoptosis, Oncogene, 7 (2008) 6407–6418.

      [72] S.N. Ayrapetyan, D.O. Carpenter, K.V. Azatian, S.S. Dadalian, D.M. Martirosyan, Extralow neurotransmitter dozes-induced triggering of neuronal intracellular messanger systems, Cellular Signalization, P.G. Kostyuk, M.A. Ostrovskii, Moscow: Nauka, 1992; 89-96.

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    Nikoghosyan, A., Heqimyan, A., & Ayrapetyan, S. N. (2015). Primary mechanism responsible for age-dependent neuronal dehydration. International Journal of Basic and Applied Sciences, 5(1), 5-14. https://doi.org/10.14419/ijbas.v5i1.5388

    Received date: 2015-09-30

    Accepted date: 2015-11-21

    Published date: 2015-12-09