ssmuБюллетень сибирской медициныBulletin of Siberian Medicine1682-03631819-3684Siberian State Medical University, the Ministry of Healthcare of the Russian Federationssmu-364Research ArticleМАТЕРИАЛЫ 10-ГО МЕЖДУНАРОДНОГО КОНГРЕССА «РЕГУЛЯЦИЯ ОБЪЕМА КЛЕТКИ: НОВЫЕ ТЕРАПЕВТИЧЕСКИЕ МИШЕНИ И ФАРМАКОЛОГИЧЕСКИЕ ПОДХОДЫ»ПОИСК СЕНСОРОВ ОБЪЕМА КЛЕТОК: ПОСЛЕДНИЕ ДОСТИЖЕНИЯSEARCH FOR CELL VOLUME SENSORS: AN UPDATEOrlovS. N.OrlovS. N.sergei.n.orlov@umontreal.caGrygorszykR.GrygorszykR.sergei.n.orlov@umontreal.caCentre de recherche, Centre hospitalier de l’Université de Montréal (CRCHUM), Montreal, PQ, Canada; Faculty of Biology, M.V. Lomonosov Moscow State University, Moscow, Russian Federation; Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, MoscowRussian FederationCentre de recherche, Centre hospitalier de l’Université de Montréal (CRCHUM), Montreal, PQCanada2013280820131241323Copyright © Orlov S.N., Grygorszyk R., 20132013Orlov S.N., Grygorszyk R.Orlov S.N., Grygorszyk R.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://bulletin.ssmu.ru/jour/article/view/364

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Cell volume changes affect a plethora of cellular functions including macromolecular synthesis and catabolism, cell proliferation, differentiation and death. Because of these critical roles, cells regulate their volume with <1% accuracy via compensatory mechanisms termed regulatory volume increase and regulatory volume decrease. Our review focuses on recent advances in understanding the molecular origin of up-stream sensors triggering cellular responses to volume perturbations. The analysis demonstrates a major  role  of  cytoplasmic  hydrogel  as  well  as  the  crosstalk  of  polyphosphoinositides  and  twodimensional cytoskeleton (membrane carcass) in cell volume sensing.

cell volumemembrane stretchcytoskeletonbiogelReferencesKuang, K., Yiming, M., Zhu, Z., Iserovich, P., Diecke, F.P., and Fischbarg, J. 2006. Lack of threshold for anisotonic volume regulation. J. Membrane Biol., 211, pp. 27–33.Kuang, K., Yiming, M., Zhu, Z., Iserovich, P., Diecke, F.P., and Fischbarg, J. 2006. Lack of threshold for anisotonic volume regulation. J. Membrane Biol., 211, pp. 27–33.Lang, F., Busch, G., Ritter, M., Volkl, H., Waldegger, S., Gulbins, E., and Haussinger, D. 1998. Functional significance of cell volume regulatory mechanisms. Physiol. Rev., 78, pp. 247–306.Lang, F., Busch, G., Ritter, M., Volkl, H., Waldegger, S., Gulbins, E., and Haussinger, D. 1998. Functional significance of cell volume regulatory mechanisms. Physiol. Rev., 78, pp. 247–306.Lang, F. Mechanisms and significance of cell volume regulation. J. Am. Coll. Nutr., 2009, 26, pp. 613S–623S.Lang, F. Mechanisms and significance of cell volume regulation. J. Am. Coll. Nutr., 2009, 26, pp. 613S–623S.Mongin, A.A. and Orlov, S.N. Mechanisms of cell volume regulation and possible nature of the cell volume sensor. Pathophysiology, 2001, 8, pp. 77-88.Mongin, A.A. and Orlov, S.N. Mechanisms of cell volume regulation and possible nature of the cell volume sensor. Pathophysiology, 2001, 8, pp. 77-88.Hoffmann, E.K. and Simonsen, L.O. Membrane mechanisms in volume and pH regulation in vertebrate cells. Physiol. Rev., 1989, 69, pp. 315–82.Hoffmann, E.K. and Simonsen, L.O. Membrane mechanisms in volume and pH regulation in vertebrate cells. Physiol. Rev., 1989, 69, pp. 315–82.O'Neill, W.C. Physiological significance of volume- regulated transporters. Am. J. Physiol., 1999, 276, C995–C1011.O'Neill, W.C. Physiological significance of volume- regulated transporters. Am. J. Physiol., 1999, 276, C995–C1011.Hoffmann, E.K., Lambert, I.H., and Pedersen, S.F. Physiology of cell volume regulation in vertebrates. Physiol. Rev., 2009, 89, pp. 193–277.Hoffmann, E.K., Lambert, I.H., and Pedersen, S.F. Physiology of cell volume regulation in vertebrates. Physiol. Rev., 2009, 89, pp. 193–277.Strange, K. Cellular volume homeostasis. Adv. Physiol. Educ., 2004, 28, pp. 155–159.Strange, K. Cellular volume homeostasis. Adv. Physiol. Educ., 2004, 28, pp. 155–159.Delpire, E. and Austin, T.M. Kinase regulation of Na+-K+2Cl- cotransport in primary neurons. J. Physiol., 2010, 588, pp. 3365–3373.Delpire, E. and Austin, T.M. Kinase regulation of Na+-K+2Cl- cotransport in primary neurons. J. Physiol., 2010, 588, pp. 3365–3373.Koivusalo, M., Kapus, A., and Grinstein, S. Sensors, transducers, and effecgtors that regulate cell size and shape. J. Biol. Chem., 2009, 284, pp. 6595–6599.Koivusalo, M., Kapus, A., and Grinstein, S. Sensors, transducers, and effecgtors that regulate cell size and shape. J. Biol. Chem., 2009, 284, pp. 6595–6599.Pedersen, S.F., Kapus, A., and Hoffmann, E.K. Osmosensory mechanisms in cellular and systematic volume regulation. J. Am. Soc. Nephrol., 2011, 22, pp. 1587–1597.Pedersen, S.F., Kapus, A., and Hoffmann, E.K. Osmosensory mechanisms in cellular and systematic volume regulation. J. Am. Soc. Nephrol., 2011, 22, pp. 1587–1597.Macknight, A.D.C. and Leaf, A. Regulation of cellular volume. Physiol.Rev., 1977, 57, pp. 510–573.Macknight, A.D.C. and Leaf, A. Regulation of cellular volume. Physiol.Rev., 1977, 57, pp. 510–573.Kinnunen, P.K.J. Lipid bilayers as osmotic reseponse elements. Cell. Physiol. Biochem., 200, 10, pp. 243–250.Kinnunen, P.K.J. Lipid bilayers as osmotic reseponse elements. Cell. Physiol. Biochem., 200, 10, pp. 243–250.Sachs, F. Stretch-activated ion channels: what are they? Physiology, 2010, 25, pp. 50–56.Sachs, F. Stretch-activated ion channels: what are they? Physiology, 2010, 25, pp. 50–56.Callies, C., Fels, J., Liashkovich, I., Kliche, K., Jeggle, P., Kusche-Vihrog, K., and Oberleithner, H. Membrane poten- tial depolarization decreases the stiffness of vascular endothelial cells. J. Cell Sci., 2011, 124, pp. 1936–1942.Callies, C., Fels, J., Liashkovich, I., Kliche, K., Jeggle, P., Kusche-Vihrog, K., and Oberleithner, H. Membrane poten- tial depolarization decreases the stiffness of vascular endothelial cells. J. Cell Sci., 2011, 124, pp. 1936–1942.O'Neil, R.G. and Heller, S. The mechanosensitive nature of TRPV channels. Pfluger Arch.- Eur. J. Physiol., 451, 2005, pp. 193–203.O'Neil, R.G. and Heller, S. The mechanosensitive nature of TRPV channels. Pfluger Arch.- Eur. J. Physiol., 451, 2005, pp. 193–203.Pedersen, S.F. and Nilius, B. Transient receptor potential channels in mechanosensing and cell volume regulation. Methods Enzymol., 2007, 428, pp. 183–207.Pedersen, S.F. and Nilius, B. Transient receptor potential channels in mechanosensing and cell volume regulation. Methods Enzymol., 2007, 428, pp. 183–207.Martinac, B. Bacterial mechanosensitive channels as a paradigm for mechanosensory transduction. Cell. Physiol. Biochem., 2011, 28, pp. 1051–1060.Martinac, B. Bacterial mechanosensitive channels as a paradigm for mechanosensory transduction. Cell. Physiol. Biochem., 2011, 28, pp. 1051–1060.Strotmann, R., Harteneck, C., Nunnenmacher, K., Schultz, G., and Plant, T.D. OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity. Nat. Cell Biol., 2000, 2, pp. 695–702.Strotmann, R., Harteneck, C., Nunnenmacher, K., Schultz, G., and Plant, T.D. OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity. Nat. Cell Biol., 2000, 2, pp. 695–702.Spagnoli, C., Beyder, A., Besch, S., and Sachs, F. Atomic force microscopy analysis of cell volume regulation. Phys. Rev. E Stat Nonlin. Soft Matter. Phys., 2008, 78 (3 Pt 1), 78.031916.Spagnoli, C., Beyder, A., Besch, S., and Sachs, F. Atomic force microscopy analysis of cell volume regulation. Phys. Rev. E Stat Nonlin. Soft Matter. Phys., 2008, 78 (3 Pt 1), 78.031916.Oberleithner, H. and de Wardener, H.E. Sodium: A wolf in sheep's clothing. Blood Purif., 2011, 31, pp. 82–85.Oberleithner, H. and de Wardener, H.E. Sodium: A wolf in sheep's clothing. Blood Purif., 2011, 31, pp. 82–85.Boudreault, F. and Grygorczyk, R. Cell swelling-induced ATP release and gadolinium-sensitive channels. Am. J. Physiol., 2002, 282, pp. C219–C226.Boudreault, F. and Grygorczyk, R. Cell swelling-induced ATP release and gadolinium-sensitive channels. Am. J. Physiol., 2002, 282, pp. C219–C226.Hua, S.X., Gottlieb, P.A., Heo, J., and Sachs, F. A mechanosensitive ion channel regulation cell volume. Am. J. Physiol. Cell Physiol., 2010, 298, pp. C1424–C1430.Hua, S.X., Gottlieb, P.A., Heo, J., and Sachs, F. A mechanosensitive ion channel regulation cell volume. Am. J. Physiol. Cell Physiol., 2010, 298, pp. C1424–C1430.Bezanilla, F. How membrane proteins sens voltage. Nat. Rev. Mol. Cell Biol., 2008, 9, pp. 323–332.Bezanilla, F. How membrane proteins sens voltage. Nat. Rev. Mol. Cell Biol., 2008, 9, pp. 323–332.Boudreault, F. and Grygorczyk,R. 2004. Evaluation of rapid volume changes of substrate-adherent cells by conventional microscopy 3D imaging. J. Microscopy, 215, pp. 302–312.Boudreault, F. and Grygorczyk,R. 2004. Evaluation of rapid volume changes of substrate-adherent cells by conventional microscopy 3D imaging. J. Microscopy, 215, pp. 302–312.Fels, J., Orlov, S.N., and Grygorczyk, R. The hydrogel nature of mammalian cytoplasm contributes to osmosensing and extracellular pH sensing. Biophys. J., 2009, 96, pp. 4276–4285.Fels, J., Orlov, S.N., and Grygorczyk, R. The hydrogel nature of mammalian cytoplasm contributes to osmosensing and extracellular pH sensing. Biophys. J., 2009, 96, pp. 4276–4285.Groulx, N., Boudreault, F., Orlov, S.N., and Grygorczyk, R. Membrane reserves and hypotonic cell swelling. J. Membr. Biol., 2006, 214, pp. 43–56.Groulx, N., Boudreault, F., Orlov, S.N., and Grygorczyk, R. Membrane reserves and hypotonic cell swelling. J. Membr. Biol., 2006, 214, pp. 43–56.Hoffmann, E.K. Intracellular signaling involved in volume regulatory decrease. Cell. Physiol. Biochem., 2000, 10, pp. 273–288.Hoffmann, E.K. Intracellular signaling involved in volume regulatory decrease. Cell. Physiol. Biochem., 2000, 10, pp. 273–288.Parshina, E.Y., Yusipovich, A.I., Platonova, A.A., Grygorczyk, R., Maksimov, G.V., and Orlov, S.N. Thermal inactivation of volume-sensitive K+,Clcotransport and plasma membrane relief changes in human eyrthrocytes. Pfluger Arch.Eur. J. Physiol., 2013, in press.Parshina, E.Y., Yusipovich, A.I., Platonova, A.A., Grygorczyk, R., Maksimov, G.V., and Orlov, S.N. Thermal inactivation of volume-sensitive K+,Clcotransport and plasma membrane relief changes in human eyrthrocytes. Pfluger Arch.Eur. J. Physiol., 2013, in press.Kageyama, K., Onoyama, Y., Kogawa, H., Goto, E., and Tanabe, K. The maximum and minimum water content and cell volume of human erythrocytes in vitro. Biophys. Chem., 1989, 34, pp. 79–82.Kageyama, K., Onoyama, Y., Kogawa, H., Goto, E., and Tanabe, K. The maximum and minimum water content and cell volume of human erythrocytes in vitro. Biophys. Chem., 1989, 34, pp. 79–82.Gillespie, P.G. and Walker, R.G. Molecular basis of mechanosensory transduction. Nature, 2001, 413, pp. 194–202.Gillespie, P.G. and Walker, R.G. Molecular basis of mechanosensory transduction. Nature, 2001, 413, pp. 194–202.vom Dahl, S., Schliess, F., Reissmann, R., Gorg, B., Weiergraber, O., Kocalkova, M., Dombrowski, F., and Haussinger, D. Involvement of integrins in osmosensing and signaling toward autophagic proteolysis in rat liver. J. Biol. Chem., 2003, 278, pp. 27088–27095.vom Dahl, S., Schliess, F., Reissmann, R., Gorg, B., Weiergraber, O., Kocalkova, M., Dombrowski, F., and Haussinger, D. Involvement of integrins in osmosensing and signaling toward autophagic proteolysis in rat liver. J. Biol. Chem., 2003, 278, pp. 27088–27095.Schliess, F. and Haussinger, D. Osmosensing by integrins in rat liver. Methods Enzymol., 2007, 428, pp. 129–144.Schliess, F. and Haussinger, D. Osmosensing by integrins in rat liver. Methods Enzymol., 2007, 428, pp. 129–144.Browe, D.M. and Baumgarten, C.M. Angiotensin II (AT1) receptors and NADH oxidase regulate Clcurrent elicited by beta1 integrin stretch in rabbit ventricular myocytes. J. Gen. Physiol., 2004, 124, pp. 273–287.Browe, D.M. and Baumgarten, C.M. Angiotensin II (AT1) receptors and NADH oxidase regulate Clcurrent elicited by beta1 integrin stretch in rabbit ventricular myocytes. J. Gen. Physiol., 2004, 124, pp. 273–287.Moeckel, G.W., Zhang, L., Chen, X., Rossini, M., Zent, R., and Pozzi, A. Role of integrin  in the regulation of renal medullary osmolyte concentration. Am. J. Physiol. Renal Physiol., 2013, 290, pp. F223–F231.Moeckel, G.W., Zhang, L., Chen, X., Rossini, M., Zent, R., and Pozzi, A. Role of integrin  in the regulation of renal medullary osmolyte concentration. Am. J. Physiol. Renal Physiol., 2013, 290, pp. F223–F231.Sowa,G. 2012. Caveolae, caveolins, cavins, and endothelial cell function: new insights. Front.Physiol. 2:120.Sowa,G. 2012. Caveolae, caveolins, cavins, and endothelial cell function: new insights. Front.Physiol. 2:120.Kozera, L., White, E., and Calaghan, S. Caveolae act as membrane reserves which limit mechamosensitve I(Cl,swell) channel activation during swelling in the rat ventricular myocyte. PLoS One, 2009, 4:e8312.Kozera, L., White, E., and Calaghan, S. Caveolae act as membrane reserves which limit mechamosensitve I(Cl,swell) channel activation during swelling in the rat ventricular myocyte. PLoS One, 2009, 4:e8312.Sihna, B., Koster, D., Ruez, R., Gonnord, P., Bastiani, M., abankwa, D., Stan, R.V., Butler-Browne, G., Vedie, B., Johannes, L. et al. Cells respond to mechanical stress by rapid disassembly of caveolae. Cell, 2011, 144, pp. 402–413.Sihna, B., Koster, D., Ruez, R., Gonnord, P., Bastiani, M., abankwa, D., Stan, R.V., Butler-Browne, G., Vedie, B., Johannes, L. et al. Cells respond to mechanical stress by rapid disassembly of caveolae. Cell, 2011, 144, pp. 402–413.Trouet, D., Hermans, D., Droogmans, G., Nilius, B., and Eggermont, J. Inhibition of volume-regulated anion channels by dominant-negative caveolin-1. Biochem. Biophys. Res. Commun., 2001, 284, pp. 461–465.Trouet, D., Hermans, D., Droogmans, G., Nilius, B., and Eggermont, J. Inhibition of volume-regulated anion channels by dominant-negative caveolin-1. Biochem. Biophys. Res. Commun., 2001, 284, pp. 461–465.Eduardsen, K., Larsen, S.L., Novak, I., Lambert, I.H., Hoffmann, E.K., and Pedersen, S.F. Cell volume regulation and signaling in 3T3-L1 pre-adipocytes and adipocytes: on the possible role of caveolae, insulin receptors, FAK and ERK1/2. Cell Physiol. Biochem., 2011, 28, pp. 1231–1246.Eduardsen, K., Larsen, S.L., Novak, I., Lambert, I.H., Hoffmann, E.K., and Pedersen, S.F. Cell volume regulation and signaling in 3T3-L1 pre-adipocytes and adipocytes: on the possible role of caveolae, insulin receptors, FAK and ERK1/2. Cell Physiol. Biochem., 2011, 28, pp. 1231–1246.Lehtonen, J.V.A. and Kinnunen, P.K.J. Phospholipase A2 as a mechanosensor. Biophys. J., 1995, 68, pp. 1888–1894.Lehtonen, J.V.A. and Kinnunen, P.K.J. Phospholipase A2 as a mechanosensor. Biophys. J., 1995, 68, pp. 1888–1894.Papakonstanti, E.A., Vardaki, E.A., and Stounaras, C. Actin cytoskeleton: a signaling sensor in cell volume regulation. Cell Physiol. Biochem., 2000, 10, pp. 257–264.Papakonstanti, E.A., Vardaki, E.A., and Stounaras, C. Actin cytoskeleton: a signaling sensor in cell volume regulation. Cell Physiol. Biochem., 2000, 10, pp. 257–264.Di Ciano-Oliveira, C., Thirone, A.C.P., Szaszi, K., and Kapus, A. Osmotic stress and the cytoskeleton: the Role of Rho GTPases. Acta Physiol., 2006, 187, pp. 257–272.Di Ciano-Oliveira, C., Thirone, A.C.P., Szaszi, K., and Kapus, A. Osmotic stress and the cytoskeleton: the Role of Rho GTPases. Acta Physiol., 2006, 187, pp. 257–272.Jakab, M., Furst, J., Gschwentner, M., Botta, M., Garavaglia, M.-L., Bazzini, C., Rodighiero, S., Meyer, G., Eichmuller, S., Woll, E. et al. Mechanisms sensing and modulating signals arisng from cell swelling. Cell. Physiol. Biochem., 2002, 12, pp. 235–258.Jakab, M., Furst, J., Gschwentner, M., Botta, M., Garavaglia, M.-L., Bazzini, C., Rodighiero, S., Meyer, G., Eichmuller, S., Woll, E. et al. Mechanisms sensing and modulating signals arisng from cell swelling. Cell. Physiol. Biochem., 2002, 12, pp. 235–258.Platonova, A.A., Orlov, S.N., and Grygorczyk, R. Volume changes triggered by aniosmotic media in intact and permeabilized А 549 cells: role of cytoskeleton network. Bull. Siberian Med., 2013, in press.Platonova, A.A., Orlov, S.N., and Grygorczyk, R. Volume changes triggered by aniosmotic media in intact and permeabilized А 549 cells: role of cytoskeleton network. Bull. Siberian Med., 2013, in press.Parker, J.C. In defense of cell volume? Am. J. Physiol., 1993, 265, pp. C1191–C1200.Parker, J.C. In defense of cell volume? Am. J. Physiol., 1993, 265, pp. C1191–C1200.Orlov, S.N., Kolosova, I.A., Cragoe, E.J., Gurlo, T.G., Mongin, A.A., Aksentsev, S.L., and Konev, S.V. Kinetics and peculiarities of thermal inactivation of volumedependent Na/H exchange, Na,K,2Cl cotransport and K,Cl cotransport in rat erythrocytes. Biochim. Biophys. Acta, 1993, 1151, pp. 186–192.Orlov, S.N., Kolosova, I.A., Cragoe, E.J., Gurlo, T.G., Mongin, A.A., Aksentsev, S.L., and Konev, S.V. Kinetics and peculiarities of thermal inactivation of volumedependent Na/H exchange, Na,K,2Cl cotransport and K,Cl cotransport in rat erythrocytes. Biochim. Biophys. Acta, 1993, 1151, pp. 186–192.Brandts, J.F., Taverna, R.D., Salasivan, E., and Lysko, K.A. Calorimetric studies of structural transitions of human erythrocyte membrane. Studies of B and C transitions. Biochim. Biophys. Acta, 1978, 512, pp. 566–578.Brandts, J.F., Taverna, R.D., Salasivan, E., and Lysko, K.A. Calorimetric studies of structural transitions of human erythrocyte membrane. Studies of B and C transitions. Biochim. Biophys. Acta, 1978, 512, pp. 566–578.Shnyrov, V.L., Orlov, S.N., Zhadan, G.G., and Pokudin, N.I. Thermal inactivation of membrane proteins, volumedependent Na+,K+ cotransport, and protein kinase C activator-induced changes of the shape of human and rat erythrocytes. Biomed. Biochim. Acta, 1990, 49, pp. 445–453.Shnyrov, V.L., Orlov, S.N., Zhadan, G.G., and Pokudin, N.I. Thermal inactivation of membrane proteins, volumedependent Na+,K+ cotransport, and protein kinase C activator-induced changes of the shape of human and rat erythrocytes. Biomed. Biochim. Acta, 1990, 49, pp. 445–453.Gulak, P.V., Orlov, S.N., Pokudin, N.I., Postnov, Yu.V., Litvinov, I.S., Orlov, N.Yu., and Shnyrov, V.L. Microcalorimetry and electrophoresis of the erythrocyte membrane of spontaneously hypertensive rats. J. Hypertens., 1984, 2, pp. 81–84.Gulak, P.V., Orlov, S.N., Pokudin, N.I., Postnov, Yu.V., Litvinov, I.S., Orlov, N.Yu., and Shnyrov, V.L. Microcalorimetry and electrophoresis of the erythrocyte membrane of spontaneously hypertensive rats. J. Hypertens., 1984, 2, pp. 81–84.Orlov, S.N., Pokudin, N.I., Kotelevtsev, Yu.V., and Gulak, P.V. Volume-dependent regulation of ion transport and membrane phosphorylation in human and rat erythrocytes. J. Membrane Biol., 1989, 107, pp. 105–117.Orlov, S.N., Pokudin, N.I., Kotelevtsev, Yu.V., and Gulak, P.V. Volume-dependent regulation of ion transport and membrane phosphorylation in human and rat erythrocytes. J. Membrane Biol., 1989, 107, pp. 105–117.Orlov, S.N., Kuznetsov, S.R., Kolosova, I.A., Aksentsev, S.L., and Konev, S.V. Volume-dependent regulation of ion transporters in human and rat erythrocytes: role of cytoskeleton and protein phosphorylation. Russian Physiol. J., 1997, 83, no. 5–6, 119–147.Orlov, S.N., Kuznetsov, S.R., Kolosova, I.A., Aksentsev, S.L., and Konev, S.V. Volume-dependent regulation of ion transporters in human and rat erythrocytes: role of cytoskeleton and protein phosphorylation. Russian Physiol. J., 1997, 83, no. 5–6, 119–147.Sachs, J.R. How do red blood cells know how big they are? In Cell volume regulation: the molecular mechanism and volume sensing machinery. Y. Okada, editor. Elsevier Science, Tokyo, 1998, pp. 3–13.Sachs, J.R. How do red blood cells know how big they are? In Cell volume regulation: the molecular mechanism and volume sensing machinery. Y. Okada, editor. Elsevier Science, Tokyo, 1998, pp. 3–13.Janmey, P.A. and Lindberg, U. Cytoskeletal regulation: rich in lipids. Nat. Rev. Mol. Cell Biol., 2004, 5, pp. 658–666.Janmey, P.A. and Lindberg, U. Cytoskeletal regulation: rich in lipids. Nat. Rev. Mol. Cell Biol., 2004, 5, pp. 658–666.Nasuhoglu, C., Feng, S., Mao, Y., Shammat, I., Yamamato, M., Earnest, S., Lemmon, M., and Hilgemann, D.W. Modulation of cardiac PIP2 by cardioactive hormones and other physiologically relevant interventions. Am. J. Physiol. Cell Physiol., 2002, 283, pp. C223–C234.Nasuhoglu, C., Feng, S., Mao, Y., Shammat, I., Yamamato, M., Earnest, S., Lemmon, M., and Hilgemann, D.W. Modulation of cardiac PIP2 by cardioactive hormones and other physiologically relevant interventions. Am. J. Physiol. Cell Physiol., 2002, 283, pp. C223–C234.Yamamoto, M., Chen, M.Z., Wang, Y.J., Sun, H.Q., Wei, Y., Martinez, M., and Yin, H.L. Hypertonic stress increases phosphatidylinositol 4,5-biphosphate levels by activating PIP5KIbeta. J. Biol. Chem., 2006, 281, pp. 32630–32638.Yamamoto, M., Chen, M.Z., Wang, Y.J., Sun, H.Q., Wei, Y., Martinez, M., and Yin, H.L. Hypertonic stress increases phosphatidylinositol 4,5-biphosphate levels by activating PIP5KIbeta. J. Biol. Chem., 2006, 281, pp. 32630–32638.Nielsen, D.K., Jensen, A.K., Harbak, H., Christensen, S.C., and Simonsen, L.O. Cell content of phospatidylinositol (4,5)biphosphate in Ehrlich mouse ascites tumour cells in response to cell volume perturbations in anisotonic ans isosmotic media. J. Physiol., 2007, 582, pp. 1027–1036.Nielsen, D.K., Jensen, A.K., Harbak, H., Christensen, S.C., and Simonsen, L.O. Cell content of phospatidylinositol (4,5)biphosphate in Ehrlich mouse ascites tumour cells in response to cell volume perturbations in anisotonic ans isosmotic media. J. Physiol., 2007, 582, pp. 1027–1036.Browe, D.M. and Baumgarten, C.M. EGFR kinase regulates volume-sensitive chloride current elicited by integrin stretch via Pi-3K and NADH oxidaze in ventricular myocytes. J.Gen.Physiol., 2006, 127, pp. 237–251.Browe, D.M. and Baumgarten, C.M. EGFR kinase regulates volume-sensitive chloride current elicited by integrin stretch via Pi-3K and NADH oxidaze in ventricular myocytes. J.Gen.Physiol., 2006, 127, pp. 237–251.Lambert, I.H., Pedersen, S.F., and Poulsen, K.A. Activation of PLA2 isoforms by cell swelling and ischemia /hypoxia. Acta Physiol., 2006, 187, pp. 75–85.Lambert, I.H., Pedersen, S.F., and Poulsen, K.A. Activation of PLA2 isoforms by cell swelling and ischemia /hypoxia. Acta Physiol., 2006, 187, pp. 75–85.Wang, Y., Roman, R., Lidofsky, S.D., and Fitz, J.G. Autocrine signaling through ATP release represents a novel mechanism for cell volume regulation. Proc. Natl. Acad. Sci. USA, 1996, 93, pp. 12020–12025.Wang, Y., Roman, R., Lidofsky, S.D., and Fitz, J.G. Autocrine signaling through ATP release represents a novel mechanism for cell volume regulation. Proc. Natl. Acad. Sci. USA, 1996, 93, pp. 12020–12025.Tatur, S., Groulx, N., Orlov, S.N., and Grygorczyk, R. Ca2+dependent ATP release from A549 cells involves synergic autocrine stimulation by coreleased uridine nucleotides. J. Physiol., 2007, 584, pp. 419–435.Tatur, S., Groulx, N., Orlov, S.N., and Grygorczyk, R. Ca2+dependent ATP release from A549 cells involves synergic autocrine stimulation by coreleased uridine nucleotides. J. Physiol., 2007, 584, pp. 419–435.Hazama, A., Shimizu, T., Ando-Akatsuka, Y., Hayashi, S., Tanaka, S., Maeno, E., and Okada, Y. Swelling-induced, CFTR-dependent ATP-release from human epithelial cell line: lack of correlation with volume-sensitive Clchannels. J. Gen. Physiol., 1999, 114, pp. 525–533.Hazama, A., Shimizu, T., Ando-Akatsuka, Y., Hayashi, S., Tanaka, S., Maeno, E., and Okada, Y. Swelling-induced, CFTR-dependent ATP-release from human epithelial cell line: lack of correlation with volume-sensitive Clchannels. J. Gen. Physiol., 1999, 114, pp. 525–533.van der Wijk, T., de Jonge, H.R., and Tilly, B.C. Osmotic cell swelling-induced ATP release mediates the activation of extracellular signal-regulated protein kinese (Erk)-1/2 but not the activation of osmo-sensitive anion channels. Biochem. J., 1999, 343, pp. 579–586.van der Wijk, T., de Jonge, H.R., and Tilly, B.C. Osmotic cell swelling-induced ATP release mediates the activation of extracellular signal-regulated protein kinese (Erk)-1/2 but not the activation of osmo-sensitive anion channels. Biochem. J., 1999, 343, pp. 579–586.Mongin, A.A. and Kimelberg, H.K. ATP regulates anion channel-mediated organic osmolyte release from cultured rat astrocytes via multiple Ca2+-sensitive mechanisms. Am. J. Physiol. Cell Physiol., 2005, 288, pp. C204–C213.Mongin, A.A. and Kimelberg, H.K. ATP regulates anion channel-mediated organic osmolyte release from cultured rat astrocytes via multiple Ca2+-sensitive mechanisms. Am. J. Physiol. Cell Physiol., 2005, 288, pp. C204–C213.Koltsova, S.V., Platonova, A., Maksimov, G.V., Mongin, A.A., Grygorczyk, R., and Orlov, S.N. 2011, Activtion of P2Y receptors causes strong and persistant shrinkage of C11MDCK renal epithelial cells. Am. J. Physiol. Cell Physiol., 2011, 301, pp. C403–C412.Koltsova, S.V., Platonova, A., Maksimov, G.V., Mongin, A.A., Grygorczyk, R., and Orlov, S.N. 2011, Activtion of P2Y receptors causes strong and persistant shrinkage of C11MDCK renal epithelial cells. Am. J. Physiol. Cell Physiol., 2011, 301, pp. C403–C412.Burnstock, G. Physiology and pathophysiology of purinergic neurotransmission. Physiol. Rev., 2007, 87, pp. 659–797.Burnstock, G. Physiology and pathophysiology of purinergic neurotransmission. Physiol. Rev., 2007, 87, pp. 659–797.Holtzclaw, J.D., Liu, L., Grimm, P.R., and Sansom, S.C. Shear stress-induced volume decrease of C11-MDCK cells by BK-4/4. Am. J. Physiol. Renal Physiol., 2010, 299, pp. F507–F516.Holtzclaw, J.D., Liu, L., Grimm, P.R., and Sansom, S.C. Shear stress-induced volume decrease of C11-MDCK cells by BK-4/4. Am. J. Physiol. Renal Physiol., 2010, 299, pp. F507–F516.Heo, J., Sachs, F., Wang, J., and Hua, S.Z. Shear-induced volume decrease in MDCL cells. Cell Physiol. Biochem., 2012, 30, pp. 395–406.Heo, J., Sachs, F., Wang, J., and Hua, S.Z. Shear-induced volume decrease in MDCL cells. Cell Physiol. Biochem., 2012, 30, pp. 395–406.Minton, A.P. Excluded volume as determinant of macromolecular structure and reactivity. Biopolymers, 1981, 20, pp. 2093–2120.Minton, A.P. Excluded volume as determinant of macromolecular structure and reactivity. Biopolymers, 1981, 20, pp. 2093–2120.Fulton, A.B. How crowded is cytoplasm. Cell, 1982, 30, pp. 345–347.Fulton, A.B. How crowded is cytoplasm. Cell, 1982, 30, pp. 345–347.Minton, A.P. The influence of macromolecular crowding and macromolecular confinement on biochemical reactions in physiological media. J. Biol. Chem., 2001, 276, pp. 10577–10580.Minton, A.P. The influence of macromolecular crowding and macromolecular confinement on biochemical reactions in physiological media. J. Biol. Chem., 2001, 276, pp. 10577–10580.Ellis, R.J. Macromolecular crowding: an important but negelected aspect the intracellular environment. Curr. Opin. Struct. Biol., 2001, 11, pp. 114–119.Ellis, R.J. Macromolecular crowding: an important but negelected aspect the intracellular environment. Curr. Opin. Struct. Biol., 2001, 11, pp. 114–119.Zhou, H.-X., Rivas, G., and Minton, A.P. Macromolecular crowding and confinement: biochemical, biophysical, and potential physiological consequences. Annu. Rev. Biophys., 2008, 37, pp. 375–397.Zhou, H.-X., Rivas, G., and Minton, A.P. Macromolecular crowding and confinement: biochemical, biophysical, and potential physiological consequences. Annu. Rev. Biophys., 2008, 37, pp. 375–397.Zimmerman, S.B. and Harrison, B. Macromolecular crowding increases binding of DNA polymerase to DNA; an adaptive effect. Proc. Natl. Acad. Sci. USA, 1987, 84, pp. 1871–1875.Zimmerman, S.B. and Harrison, B. Macromolecular crowding increases binding of DNA polymerase to DNA; an adaptive effect. Proc. Natl. Acad. Sci. USA, 1987, 84, pp. 1871–1875.Minton, A.P., Colclasure, G.C., and Parker, J.C. Model for the role of macromolecular crowding in regulation of cellular volume. Proc. Natl. Acad. Sci. USA, 1992, 89, pp. 10504–10506.Minton, A.P., Colclasure, G.C., and Parker, J.C. Model for the role of macromolecular crowding in regulation of cellular volume. Proc. Natl. Acad. Sci. USA, 1992, 89, pp. 10504–10506.Colclasure, G.C. and Parker, J.C. Cytosolic protein concentration is the primary volume signal for swelling-induced K,Cl cotransport in dog red cells. J. Gen. Physiol., 1991, 100, pp. 1–10.Colclasure, G.C. and Parker, J.C. Cytosolic protein concentration is the primary volume signal for swelling-induced K,Cl cotransport in dog red cells. J. Gen. Physiol., 1991, 100, pp. 1–10.Summers, J.C., Trais, L., Lajvardi, R., Hergan, D., Buechler, R., Chang, H., Pena-Rasgado, C., and Rasgado-Flores, H. Role of concentration and size of intracellular macromolecules in cell volume regulation. Am. J. Physiol., 1997, 273, pp. C360–C370.Summers, J.C., Trais, L., Lajvardi, R., Hergan, D., Buechler, R., Chang, H., Pena-Rasgado, C., and Rasgado-Flores, H. Role of concentration and size of intracellular macromolecules in cell volume regulation. Am. J. Physiol., 1997, 273, pp. C360–C370.Platonova, A., Koltsova, S.V., Maksimov, G.V., Grygorczyk, R., and Orlov, S.N. The death of ouabaintreated renal epithelial C11-MDCK cells is not mediated by swelling-induced plasma membrane rupture. J. Membr. Biol., 2011, 241, pp. 145–154.Platonova, A., Koltsova, S.V., Maksimov, G.V., Grygorczyk, R., and Orlov, S.N. The death of ouabaintreated renal epithelial C11-MDCK cells is not mediated by swelling-induced plasma membrane rupture. J. Membr. Biol., 2011, 241, pp. 145–154.Luby-Phelps, K. Cytoarchitecture and physical peoperties of cytoplasm: volume, viscosity, diffusion, intracellular surface area. Int. Rev. Cytol., 2000, 192, pp. 189–221.Luby-Phelps, K. Cytoarchitecture and physical peoperties of cytoplasm: volume, viscosity, diffusion, intracellular surface area. Int. Rev. Cytol., 2000, 192, pp. 189–221.Brown, A. and Lasek, R.J. Neurofilaments move apart freely when released from the circumferential constrain of the axonal plasma membrane. Cell Motil. Cytroskeleton, 1993, 26, pp. 313–324.Brown, A. and Lasek, R.J. Neurofilaments move apart freely when released from the circumferential constrain of the axonal plasma membrane. Cell Motil. Cytroskeleton, 1993, 26, pp. 313–324.Platonova, A.A., Grygorczyk, R., and Orlov, S.N. Temperature dependence of volume changes triggered by anisosmotic media in intact and permeabilized A549 cells. Bull. Siberian Med., 2013, in press.Platonova, A.A., Grygorczyk, R., and Orlov, S.N. Temperature dependence of volume changes triggered by anisosmotic media in intact and permeabilized A549 cells. Bull. Siberian Med., 2013, in press.Burg ,M.B., Ferraris, J.D., and Dmitrieva, N.I. Cellular response to hyperosmotic stresses. Physiol. Rev., 2007, 87, pp. 1441–1474.Burg ,M.B., Ferraris, J.D., and Dmitrieva, N.I. Cellular response to hyperosmotic stresses. Physiol. Rev., 2007, 87, pp. 1441–1474.Burg, M.B., Kwon, E.D., and Kultz, D. Regulation of gene expression by hypertonicity. Annu. Rev. Physiol., 1997, 59, pp. 437–455.Burg, M.B., Kwon, E.D., and Kultz, D. Regulation of gene expression by hypertonicity. Annu. Rev. Physiol., 1997, 59, pp. 437–455.Sheikh-Hamad, D. and Gustin, M.C. MAP kinases and the adaptive response to hypertonicity: functional preservation from yeast to mammals. Am. J. Physiol. Renal Physiol. 2004, 287, pp. F1102–F1110.Sheikh-Hamad, D. and Gustin, M.C. MAP kinases and the adaptive response to hypertonicity: functional preservation from yeast to mammals. Am. J. Physiol. Renal Physiol. 2004, 287, pp. F1102–F1110.Koltsova, S.V., Trushina, Y., Haloui, M., Akimova, O.A., Tremblay, J., Hamet, P., and Orlov, S.N. Ubiquitous [Na+]i/[K+]i-sensitive transcriptome in mammalian cells: evidence for Ca2+i-independent excitation-transcription coupling. PLoS One, 2012, 7, e38032.Koltsova, S.V., Trushina, Y., Haloui, M., Akimova, O.A., Tremblay, J., Hamet, P., and Orlov, S.N. Ubiquitous [Na+]i/[K+]i-sensitive transcriptome in mammalian cells: evidence for Ca2+i-independent excitation-transcription coupling. PLoS One, 2012, 7, e38032.

The authors declare that there are no conflicts of interest present.