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 OJBIPHY  Vol.10 No.2 , April 2020
The Quantum-Mechanical Sensitive Na/K Pump Is a Key Mechanism for the Metabolic Control of Neuronal Membrane Function
Abstract: 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.
Cite this paper: Ayrapetyan​, S. (2020) The Quantum-Mechanical Sensitive Na/K Pump Is a Key Mechanism for the Metabolic Control of Neuronal Membrane Function. Open Journal of Biophysics, 10, 59-83. doi: 10.4236/ojbiphy.2020.102006.
References

[1]   Hodgkin, A.L. (1964) The Consecution of the Nervous Impulse. University Press, Liverpool.

[2]   Katz, B. (1966) Nerve, Muscle and Synapse. Raven Press, New York.

[3]   Skou, J.C. (1957) The Influence of Some Cations on an Adenosine Triphosphatase from Peripheral Nerves. Biochimica et Biophysica Acta, 23, 394-401.
https://doi.org/10.1016/0006-3002(57)90343-8

[4]   Thomas, R.C. (1972) Electrogenic Sodium Pump in Nerve and Muscle Cells. Physiological Reviews, 52, 563-594.
https://doi.org/10.1152/physrev.1972.52.3.563

[5]   Kerkut, G.A. and Thomas, R.C. (1965) An Electrogenic Sodium Pump in Snail Nerve Cells. Comparative Biochemistry and Physiology, 14, 167-183.
https://doi.org/10.1016/0010-406X(65)90017-4

[6]   Thomas, R.C. (1969) Membrane Current and Intracellular Sodium Changes in a Snail Neuron during Extrusion of Injected Sodium. The Journal of Physiology, 201, 495-514.
https://doi.org/10.1113/jphysiol.1969.sp008769

[7]   Grundfest, H., Kao, C.Y. and Mirano, M.A. (1954) Bioelectric Effect of Ions Microinjected into the Giant Axon of Loligo. Journal of General Physiology, 38, 245-282.
https://doi.org/10.1085/jgp.38.2.245

[8]   Ayrapetyan, S.N. (1969) Metabolically Dependent Fraction of Membrane Potential and Electrode Properties of the Membrane of Giant Neurons in Mollusks. Biofizika, 14, 1027-1031.

[9]   Gorman, A.L. and Marmor, M.F. (1970) Contribution of Sodium Pump and Ionic Gradients to the Membrane Potential of Molluscan Neuron. Physiology, 210, 897-917.
https://doi.org/10.1113/jphysiol.1970.sp009248

[10]   Ayrapetyan, S.N., Nasarenko, A.R. and Sorokina, Z.A. (1970) Dependency of Active Ion Transport in Snail Neurons of Ionic Composition of Extracellular Medium. Biofizika, 16, 1037-1042.

[11]   Ayrapetyan, G., Ayrapetyan, S. and Carpenter, D. (1991) The Electrogenic Sodium Pump Activity in Aplysia Neuron Is Not Potential-Dependent. Acta Biological Hungarica, 50, 27-34.

[12]   Carpenter, D.O. and Alving, B.O. (1968) A Contribution of an Electrogenic Na+ Pump to Membrane Potential in Aplysia Neurons. Journal of General Physiology, 52, 1-21.
https://doi.org/10.1085/jgp.52.1.1

[13]   Carpenter, D.O. (1970) Membrane Potential Produced Directly by the Na Pump in Aplysia Neurons. Comparative Biochemistry and Physiology, 35, 371-385.
https://doi.org/10.1016/0010-406X(70)90602-X

[14]   Ayrapetyan, S.N. (1969) Effect of Temperature on Membrane Potential of Giant Neurons in Snails. Biofizika, 14, 663-668.
https://doi.org/10.1007/BF01124277

[15]   Ayrapetyan, S.N. (1969) Mechanism of Regulation of Spontaneous Activity of Snail Giant Neurons. Biofizika, 14, 866-872. (In Russian)

[16]   Kay, A.R. and Blaustein, M.P. (2019) Evolution of Our Understanding of Cell Volume Regulation by the Pump-Leak Mechanism. Journal of General Physiology, 151, 407-416.
https://doi.org/10.1085/jgp.201812274

[17]   Hoffmann, E.K., Lambert, I.H. and Pedersen, S.F. (2009) Physiology of Cell Volume Regulation in Vertebrates. Physiological Reviews, 89, 193-277.
https://doi.org/10.1152/physrev.00037.2007

[18]   Ayrapetyan, S.N., Suleymanyan, M.A., Sagian, A.A. and Dadalyan, S.S. (1984) Autoregulation of Electrogenic Sodium Pump. Cellular and Molecular Neurobiology, 4, 367-384.
https://doi.org/10.1007/BF00733598

[19]   Carpenter, D.O., Fejtl, M., Ayrapetyan, S.N., Szarowski, D.H. and Turner, J.N. (1992) Dynamic Changes in Neuronal Volume Resulting from Osmotic and Sodium Transport Manipulations. Acta Biologica Hungarica, 43, 39-48.

[20]   Palade, G.E. (1953) Fine Structure of Blood Capillaries. Journal of Applied Physics, 24, 1424-1432.

[21]   Parton, R.G. and Simons, K. (2007) The Multiple Faces of Caveolae. Nature Reviews, 8, 185-194.
https://doi.org/10.1038/nrm2122

[22]   Cooke, K.R. (1981) Ouabain and Regulation of Cellular Volume in Slices of Mammalian Renal Cortex. The Journal of Physiology, 320, 319-332.
https://doi.org/10.1113/jphysiol.1981.sp013952

[23]   Cooke, K.R. (1978) Ouabain and Regulation of Cellular Volume in Freshly Prepared Slices of Rabbit Renal Cortex. The Journal of Physiology, 279, 361-374.
https://doi.org/10.1113/jphysiol.1978.sp012349

[24]   Ayrapetyan, S.N. and Suleymanian, M.A. (1979) On the Pump-Induced Cell Volume Changes. Comparative Biochemistry and Physiology, 64A, 571-575.
https://doi.org/10.1016/0300-9629(79)90585-1

[25]   Bloedel, J., Gage, P.W., Llinás, R. and Quastel, D.M. (1966) Transmitter Release at the Squid Giant Synapse in the Presence of Tetrodotoxin. Nature, 212, 49-50.
https://doi.org/10.1038/212049a0

[26]   Iwasa, K., Tasaki, I. and Gibbons, R.C. (1980) Swelling of Nerve Fibers Associated with Action Potentials. Science, 210, 338-339.
https://doi.org/10.1126/science.7423196

[27]   Terakawa, S. (1990) Intracellular Pressure and the Excitable Membrane. In: Ayrapetyan, S.N., Ed., Metabolic Regulation of Membrane Function, Academy of Sciences of Armenian SSR Publishing, Yerevan, 140-148.

[28]   Kojima, M., Ayrapetyan, S. and Koketsu K. (1984) On the Membrane Potential Independent Mechanism of Sodium Pump-Induced Inhibition of Spontaneous Electrical Activity of Japanese Land Snail Neurons. Comparative Biochemistry and Physiology, 77, 577-583.
https://doi.org/10.1016/0300-9629(84)90232-9

[29]   Ayrapetyan, S.N., Rychkov, G.Y. and Suleymanyan, M.A. (1988) Effects of Water Flow on Transmembrane Ionic Currents in Neurons of Helix Pomatia and in Squid Giant Axon. Comparative Biochemistry and Physiology, 89, 179-186.
https://doi.org/10.1016/0300-9629(88)91076-6

[30]   Rychkov, G.Y., Suleymanian, M.A. and Ayrapetyan, S.N. (1989) The Dependence of Water Flow Effect on the Ionic Currents of Dialyzed Neuron on Fluidity of Somatic Membrane. Biological Membranes, 6, 733-740. (In Russian)

[31]   Suleymanian, M.A., Ayrapetyan, S.N., Arakelyan, V.B. and Ayrapetyan, V.Y. (1993) The Effect of Osmotic Gradient on the Outward Potassium Current in Dialyzed Neurons of Helix Pomatia. Cellular and Molecular Neurobiology, 13, 183-190.
https://doi.org/10.1007/BF00735374

[32]   Baker, P.F., Hodgkin, A.L. and Shaw, T.I. (1962) The Effects of Changes in Internal Ionic Concentrations on the Electrical Properties of Perfused Giant Axons. The Journal of Physiology, 164, 355-374.
https://doi.org/10.1113/jphysiol.1962.sp007026

[33]   Ayrapetyan, S.N. (1985) Activation and Inactivation Effect of the Transmembrane Water Flows on the Transmembrane Currents in Squid Giant Axon. Biological Journal of Armenia, 38, 245-250.

[34]   Keynes, R.D. (1965) Energy Transformations in the Generation of Bioelectricity. In: Chance, B., Estabrook, R.W. and Williamson, J.R., Eds., Control of Energy Metabolism, Academic Press, New York, 375-381.
https://doi.org/10.1016/B978-1-4832-3161-7.50046-X

[35]   Mullins, L.J. and Awad, M.Z. (1965) The Control of the Membrane Potential of Muscle Fibers by the Sodium Pump. Journal of General Physiology, 48, 761-775.
https://doi.org/10.1085/jgp.48.5.761

[36]   Venosa, R.A. (1978) Stimulation of the Na+-Pump by Hypotonic Solutions in Skeletal Muscle. Biochimica et Biophysica Acta, 510, 378-383.
https://doi.org/10.1016/0005-2736(78)90038-X

[37]   Ayrapetyan, S.N. (1976) Involvement of the Na Pump in Slow Oscillations Underlying the Bursting Patterns in Helix Neurons. In: Salanki, J., Ed., Neurobiology of Invertebrates, Academiai Kiado, Budapest, 353-370.

[38]   Ayrapetyan, S.N., Arvanov, V.L., Maginyan, S.B. and Azatyan, K.V. (1985) Further Study of the Correlation between Na-pump Activity and Membrane Chemosensitivity. Cellular and Molecular Neurobiology, 5, 231-243.
https://doi.org/10.1007/BF00711009

[39]   Pivavarov, A.S., Calahorro, F. and Walker, R.J. (2019) Na/K Pump and Neurotrasmitters Membrane Receptor. Invertebrate Neuroscience, 19, 1-27.
https://doi.org/10.1007/s10158-018-0221-7

[40]   Baker, P.F., Blaustein, M.P., Hodgkin, A.L. and Steinhardt, S.A. (1969) The Influence of Ca on Na Efflux in Squid Axons. The Journal of Physiology, 200, 431-458.
https://doi.org/10.1113/jphysiol.1969.sp008702

[41]   Juhaszova, M. and Blaustein, M. (1982) Na+ Pump Low and High Ouabain Affinity Alpha Subunit Isoforms Are Differently Distributed in Cells. Proceedings of The National Academy of Sciences of the United States of America, 94, 1800-1805.
https://doi.org/10.1073/pnas.94.5.1800

[42]   Blaustein, M.P. and Lederer, W.J. (1999) Na/Ca Exchange. Its Physiological Implications. Physiological Reviews, 79, 763-854.
https://doi.org/10.1152/physrev.1999.79.3.763

[43]   Sagian, A.A., Ayrapetyan, S.N. and Carpenter, D.O. (1996) Low Dose of Ouabain Stimulates the Na:Ca Exchange in Helix Neurons. Cellular and Molecular Neurobiology, 16, 180-192.
https://doi.org/10.1007/BF02150229

[44]   Ayrapetyan, S. (2012) Cell Hydration as a Universal Marker for Detection of Environmental Pollution. Environmentalist, 32, 210-221.
https://doi.org/10.1007/s10669-011-9380-3

[45]   Dadalyan, S.S., Kiss, T., Azatyan, K.V., Ayrapetyan, S.N. and Salanki, J. (1988) The Effect of Low Concentration of GABA on the ACH Sensitivity of Snail Neurons. In: Salanki, J., Ed., Neurobiology of Invertebrates, AcademiaiKiado, Budapest, 643-653.

[46]   Ayrapetyan, S. and Carpenter, D.O. (1991) On the Modulatory Role of Extra-Low Concentrations of Synaptic Transmitters for Membrane Functional Activity. Journal of Evolutionary Biochemistry and Physiology, 26, 513-528.

[47]   Ayrapetyan, S.N. (2006) Cell Aqua Medium as a Preliminary Target for the Effect of Electromagnetic Fields. In: Ayrapetyan, S.N. and Markov, M.S., Eds., Bioelectromagnetics: Current Concepts. NATO Security through Science Series, Springer Press, Netherlands, 31-64.
https://doi.org/10.1007/1-4020-4278-7_3

[48]   Ayrapetyan, S.N. (2015) The Role of Cell Hydration in Realization of Biological Effects of Non-Ionizing Radiation (NIR). Electromagnetic Biology and Medicine, 34, 197-210.
https://doi.org/10.3109/15368378.2015.1076443

[49]   Clark, R.B. (2013) Profile of Kobilka BK, Lefkowitz RJ. Nobel Laureates in Chemistry. Proceedings of The National Academy of Sciences of The United States of America, 110, 5274-5275.
https://doi.org/10.1073/pnas.1221820110

[50]   Xie, Z. and Askari, A. (2002) Na/K- ATPase as a Signal Transducer. European Journal of Biochemistry, 269, 2434-2439.
https://doi.org/10.1046/j.1432-1033.2002.02910.x

[51]   Askari, A. (2019) The Sodium Pump and Digitalis Drugs: Dogmas and Fallacies. Pharmacology Research & Perspectives, 2019, e00505.
https://doi.org/10.1002/prp2.505

[52]   Ayrapetyan, S.N., Avanesian, A.S., Avetisian TH and Majinian, S.B. (2017) Physiological Effects of Magnetic Fields May Be Mediated through Actions on the State of Calcium Ions in Solution. In: Carpenter, D. and Ayrapetyan, S., Eds., Biological Effects of Electric and Magnetic Fields, Volume 1, Academic Press, New York, 181-192.
https://doi.org/10.1016/B978-0-12-160261-1.50012-2

[53]   Ayrapetyan, S. (2013) Na+/K+Pump α3 Isoform is a Universal Membrane Sensor for Weak Environmental Signals. Journal of Bioequivalence & Bioavailability, 5, 31-40.
https://doi.org/10.4172/jbb.1000131

[54]   Brini, M. and Carifolly, E. (2009) Calcium Pumps in Health and Disease. Physiological Reviews, 9, 1341-1378.
https://doi.org/10.1152/physrev.00032.2008

[55]   Ayrapetyan, S. (2001) Na-K Pump and Na:Ca Exchanger as Metabolic Regulators and Sensors for Extra-Weak Signals in Neuromembrane. In: Ayrapetyan, S.N. and North, A.C.T., Eds., Modern Problems of Cellular and Molecular Biophysics, Noyantapan, Yerevan, 31-57.

[56]   Azatian, K.V., Karapetian, I.C. and Ayrapetyan, S.N. (1993) Effect of Low Dose Acetylcholine on Ca Ions Influx into Helix Pomatia Neurons. Biological Membranes, 10, 317-320.

[57]   Azatian, K.V., Ayrapetyan, S.N. and Carpenter, D.O. (1997) Metabotropic GABA Receptors Regulate Acetylcholine Responses on Snail Neurons. General Pharmacology, 29, 67-72.
https://doi.org/10.1016/S0306-3623(96)00568-X

[58]   Saghian, A.A., Dadalian, S.S., Takenaka, T., Suleymanian, M. and Ayrapetyan, S.N. (1986) The Effect of Short-Chain Fatty Acids on the Neuronal Membrane Function. 3. The Na Efflux from the Cells. Cellular and Molecular Neurobiology, 6, 397-405.
https://doi.org/10.1007/BF00711408

[59]   Arvanov, V.L., Takenaka, T., Dadalian, S.S. and Ayrapetyan, S.N. (1986) The Effect of Short-Chain Fatty Acids on the Neuronal Membrane Functions of Helix fPomatia. 2. Cholinoreceptive Properties. Cellular and Molecular Neurobiology, 6, 165-175.
https://doi.org/10.1007/BF00711068

[60]   Suleymanian, M., Takenaka. T., Stamboltsyan, K. and Ayrapetyan, S. (1986) The Effect of Short-Chain Fatty Acids on the Neuronal Membrane Functions of Helix Pomatia. Cellular and Molecular Neurobiology, 6, 151-163.
https://doi.org/10.1007/BF00711067

[61]   Ayrapetyan, S., Yeganyan, L., Bazikyan, G., Muradyan, R. and Arsenyan, F. (2012) Na+/K+ Pump α3 Isoform-Dependent Cell Hydration Controlling Signaling System Dysfunction as a Primary Mechanism for Carcinogenesis. Journal of Bioequivalence & Bioavailability, 4, 112-120.
https://doi.org/10.4172/jbb.1000123

[62]   Dvoretsky, A.I., Ayrapetyan, S.N. and Shainskaya, A.M. (2012) High-Affinity Ouabain Receptors: Primary Membrane Sensors for Ionizing Radiation. The Environmentalist, 32, 242-248.
https://doi.org/10.1007/s10669-012-9393-6

[63]   Mikaelyan, Y. and Ayrapetyan, S. (2019) Over-Expression of Na/Ca Exchangers in Soft Tissues as a Novel Diagnostic Marker for Carcinogenesis. Cancer Research and Molecular Mechanisms, 5.

[64]   Mikaelyan, Y., Eloyan, N. and Ayrapetyan, S. (2019) The Na/Ca Exchange as a Target for Antitumor Effect of 4Hz Pulsing Magnetic Field. Electromagnetic Biology and Medicine, 219, 1-9.
https://doi.org/10.1080/15368378.2019.1685542

[65]   Narinyan, L. and Ayrapetyan S. (2019) Age-Dependent Comparative Study of 4Hz and 8Hz EMF Exposure on Heart Muscle Tissue Hydration of Rats. Open Journal of Biophysics, 9, 70-82.
https://doi.org/10.4236/ojbiphy.2019.91005

[66]   Narinyan, L., Ayrapetyan, G. and Ayrapetyan, S. (2013) Age-Dependent Magnetosensitivity of Heart Muscle Ouabain Receptors. Bioelectromagnetics, 34, 312-322.
https://doi.org/10.1002/bem.21769

[67]   Narinyan, L. and Ayrapetyan, S. (2019) Age-Dependent Impairment of Heart Muscle Contractility as a Primary Mechanism for Overexpression of Na/Ca Exchanger in Brain Cortex Tissues. European Journal of Biophysics, 7, 27-42.

[68]   Nikoghosyan, A., Heqimyan, A. and Ayrapetyan, S. (2019) Aging Leads to Over-Expression of Na+/K+ Pump Units in Liver and Na+/Ca2+ Exchangers in Brain Cortex. Open Journal of Biophysics, 9, 218-237.
https://doi.org/10.4236/ojbiphy.2019.93016

 
 
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