Skip to main content

Ca2+ Signaling, Intracellular pH and Cell Volume in Cell Proliferation

The Journal of Membrane Biology volume 205, Article number: 129 (2005) Cite this article

Abstract

Mitogens control progression through the cell cycle in non-transformed cells by complex cascades of intracellular messengers, such as Ca2+ and protons, and by cell volume changes. Intracellular Ca2+ and proton concentrations are critical for linking external stimuli to proliferation, motility, apoptosis and differentiation. This review summarizes the role in cell proliferation of calcium release from intracellular stores and the Ca2+ entry through plasma membrane Ca2+ channels. In addition, the impact of intracellular pH and cell volume on cell proliferation is discussed.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Figure 1
Figure 2

References

  1. Alfonso A., Cabado A.G., Vieytes M.R., Botana L.M. 2000. Calcium-pH crosstalks in rat mast cells: cytosolic alkalinization, but not intracellular calcium release, is a sufficient signal for degranulation. Br. J. Pharmacol. 130:1809–1816

    PubMed  CAS  Article  Google Scholar 

  2. Amsler K., Donahue J.J., Slayman C.W., Adelberg E.A. 1985. Stimulation of bumetanide-sensitive K+ transport in Swiss 3T3 fibroblasts by serum and mitogenic hormones. J. Cell Physiol. 123:257–263

    PubMed  CAS  Article  Google Scholar 

  3. Anbari K., Schultz R.M. 1993. Effect of sodium and betaine in culture media on development and relative rates of protein synthesis in preimplantation mouse embryos in vitro. Mol. Reprod. Dev. 35:24–28

    PubMed  CAS  Article  Google Scholar 

  4. Antoniotti S., Lovisolo D., Fiorio Pla A., Munaron L. 2002. Expression and functional role of bTRPC1 channels in native endothelial cells. FEES Lett. 510:189–195

    PubMed  CAS  ISI  Article  Google Scholar 

  5. Bauer C.K., Schwarz J.R. 2001. Physiology of EAGK+ channels. J. Membr. Biol. 182:1–15

    PubMed  CAS  Google Scholar 

  6. Berridge M.J. 1993. Inositol trisphosphate and calcium signalling. Nature 361:315–325

    PubMed  CAS  ISI  Article  Google Scholar 

  7. Berridge M.J. 1995. Calcium signalling and cell proliferation. Bioessays 17:491–500

    PubMed  CAS  ISI  Article  Google Scholar 

  8. Berridge M.J., Bootman M.D., Lipp P. 1998. Calcium—a life and death signal. Nature 395:645–648

    PubMed  CAS  ISI  Article  Google Scholar 

  9. Bianchini L., L’Allemain G., Pouyssegur J. 1997. The p42/p44 mitogen-activated protein kinase cascade is determinant in mediating activation of the Na+/H+ exchanger (NHE1 isoform) in response to growth factors. J. Biol. Chem. 272:271–279

    PubMed  CAS  Article  Google Scholar 

  10. Blaustein M.P., Lederer W.J. 1999. Sodium/calcium exchange: its physiological implications. Physiol. Rev. 79:763–854

    PubMed  CAS  Google Scholar 

  11. Boynton A.L. 1988. Calcium and epithelial cell proliferation. Miner. Electrolyte Metab. 14:86–94

    PubMed  CAS  Google Scholar 

  12. Boynton A.L., Whitfield J.F., Isaacs R.J., Tremblay R. 1977. The control of human WI-38 cell proliferation by extracellular calcium and its elimination by SV-40 virus-induced proliferative transformation. J. Cell Physiol. 92:241–247

    PubMed  CAS  Article  Google Scholar 

  13. Boynton A.L., Whitfield J.F., Isaacs R.J. 1976. The different roles of serum and calcium in the control of proliferation of BALB/c 3T3 mouse cells. In Vitro 12:120–123

    PubMed  CAS  ISI  Google Scholar 

  14. Buess M., Engler O., Hirsch H.H., Moroni C. 1999. Search for oncogenic regulators in an autocrine tumor model using differential display PCR: identification of novel candidate genes including the calcium channel mtrp6. Oncogene 18:1487–1494

    PubMed  CAS  ISI  Article  Google Scholar 

  15. Bussolati O., Uggeri J., Belletti S., Dall’Asta V., Gazzola G.C. 1996. The stimulation of Na,K,Cl cotransport and of system A for neutral amino acid transport is a mechanism for cell volume increase during the cell cycle. FASEB J. 10:920–926

    PubMed  CAS  ISI  Google Scholar 

  16. Cannell M.B., Soeller C. 1998. Sparks of interest in cardiac excitation-contraction coupling. Trends Pharmacol. Sci. 19:16–20

    PubMed  CAS  Article  Google Scholar 

  17. Chyb S., Raghu P., Hardie R.C. 1999. Polyunsaturated fatty acids activate the Drosophila light-sensitive channels TRP and TRPL. Nature 397:255–259

    PubMed  CAS  ISI  Article  Google Scholar 

  18. Dubois J.M., Rouzaire-Dubois B. 1993. Role of potassium channels in mitogenesis. Prog. Biophys. Mol. Biol. 59:1–21

    PubMed  CAS  Article  Google Scholar 

  19. Dubois J.M., Rouzaire-Dubois B. 2004. The influence of cell volume changes on tumour cell proliferation. Eur. Biophys. J. 33:227–232

    PubMed  Article  Google Scholar 

  20. Durham A.C., Walton J.M. 1982. Calcium ions and the control of proliferation in normal and cancer cells. Biosci. Rep. 2:15–30

    PubMed  CAS  Article  Google Scholar 

  21. Edinger A.L., Thompson C.B. 2002. Akt maintains cell size and survival by increasing mTOR-dependent nutrient uptake. Mol. Biol. Cell 13:2276–2288

    PubMed  CAS  Article  Google Scholar 

  22. Ellis R.J. 2001. Macromolecular crowding: obvious but underappreciated. Trends Biochem. Sci. 26:597–604

    PubMed  CAS  Article  Google Scholar 

  23. Erecinska M., Deas J., Silver I.A. 1995. The effect of pH on glycolysis and phosphofructokinase activity in cultured cells and synaptosomes. J. Neurochem. 65:2765–2772

    PubMed  CAS  Google Scholar 

  24. Fiorio Pla A., Munaron L. 2001. Calcium influx, arachidonic acid, and control of endothelial cell proliferation. Cell Calcium 30:235–244

    PubMed  CAS  Article  Google Scholar 

  25. Fleischmann B.K., Murray R.K., Kotlikoff M.I. 1994. Voltage window for sustained elevation of cytosolic calcium in smooth muscle cells. Proc. Natl. Acad. Sci. USA 91:11914–11918

    PubMed  CAS  Article  Google Scholar 

  26. Frace A.M., Gargus J.J. 1989. Activation of single-channel currents in mouse fibroblasts by platelet-derived growth factor. Proc. Natl. Acad. Sci. USA 86:2511–2515

    PubMed  CAS  Article  Google Scholar 

  27. Garner M.M., Burg M.B. 1994. Macromolecular crowding and confinement in cells exposed to hypertonicity. Am. J. Physiol. 266:C877–C892

    PubMed  CAS  Google Scholar 

  28. Gill D.L., Patterson R.L. 2004. Toward a consensus on the operation of receptor-induced calcium entry signals. Sci. STKE. 243:39–42

    Google Scholar 

  29. Golovina V.A., Platoshyn O., Bailey C.L., Wang J., Limsuwan A., Sweeney M., Rubin L.J., Yuan J.X. 2001. Upregulated TRP and enhanced capacitative Ca2+ entry in human pulmonary artery myocytes during proliferation. Am J Physiol 280:H746–H755

    CAS  Google Scholar 

  30. Gonzalez-Gronow M., Misra U.K., Gawdi G., Pizzo S.V. 2005. Association of plasminogen with dipeptidyl peptidase IV and Na+-H+ exchanger isoform NHE3 regulates invasion of human 1-LN prostate tumor cells. J. Biol. Chem. 280:21173–21178

    Article  CAS  Google Scholar 

  31. Greber U.F., Gerace L. 1995. Depletion of calcium from the lumen of endoplasmic reticulum reversibly inhibits passive diffusion and signal-mediated transport into the nucleus. J. Cell Blot. 128:5–14

    PubMed  CAS  Article  Google Scholar 

  32. Grewal S.S., Edgar B.A. 2003. Controlling cell division in yeast and animals: does size matter? J. Biol. 2:5

    Article  Google Scholar 

  33. Griffiths J.R. 1991. Are cancer cells acidic? Br. J. Cancer 64:425–427

    CAS  Google Scholar 

  34. Grinstein S., Rotin D., Mason M.J. 1989. Na+/H+ exchange and growth factor-induced cytosolic pH changes. Role in cellular proliferation. Biochim. Biophys. Acta. 988:73–97

    PubMed  CAS  Google Scholar 

  35. Hanahan D., Weinberg R.A. 2000. The hallmarks of cancer. Cell 100:57–70

    PubMed  CAS  ISI  Article  Google Scholar 

  36. Hardie R.C., Minke B. 1993. Novel Ca2+ channels underlying transduction in Drosophila photoreceptors: implications for phosphoinositide-mediated Ca2+ mobilization. Trends Neurosci. 16:371–376

    PubMed  CAS  Article  Google Scholar 

  37. Häussinger D., Schliess F. 1999. Osmotic induction of signaling cascades: role in regulation of cell function. Biochem. Biophys. Res. Commun. 255:551–555

    PubMed  Article  Google Scholar 

  38. Hazelton B., Mitchell B., Tupper J. 1979. Calcium, magnesium, and growth control in the WI-38 human fibroblast cell. J. Cell Biol. 83:487–498

    PubMed  CAS  Article  Google Scholar 

  39. Hofmann T., Obukhov A.G., Schaefer M., Harteneck C., Gudermann T., Schultz G. 1999. Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol. Nature 397:259–263

    PubMed  CAS  ISI  Article  Google Scholar 

  40. Hofmann T., Schaefer M., Schultz G., Gudermann T. 2000. Transient receptor potential channels as molecular substrates of receptor-mediated cation entry. J. Mol. Med. 78:14–25

    PubMed  CAS  Article  Google Scholar 

  41. Humez S., Monet M., van Coppenolle F., Delcourt P., Prevarskaya N. 2004. The role of intracellular pH in cell growth arrest induced by ATP. Am. J. Physiol. 287:C1733–C1746

    CAS  Article  Google Scholar 

  42. Kahl C.R., Means A.R. 2003. Regulation of cell cycle progression by calcium/calmodulin-dependent pathways. Endocr. Rev. 24:719–736

    PubMed  CAS  Article  Google Scholar 

  43. Kanzaki M., Zhang Y.Q., Mashima H., Li L., Shibata H., Kojima I. 1999. Translocation of a calcium-permeable cation channel induced by insulin-like growth factor-I. Nat. Cell Biol. 1:165–170

    PubMed  CAS  Article  Google Scholar 

  44. Kapus A., Grinstein S., Wasan S., Kandasamy R., Orlowski J. 1994. Functional characterization of three isoforms of the Na+/H+ exchanger stably expressed in Chinese hamster ovary cells. ATP dependence, osmotic sensitivity, and role in cell proliferation. J. Biol. Chem. 269:23544–23552

    PubMed  CAS  Google Scholar 

  45. Lagana A., Vadnais J., Le P.U., Nguyen T.N., Laprade R., Nabi I.R., Noel J. 2000. Regulation of the formation of tumor cell pseudopodia by the Na+/H+ exchanger NHE1. J. Cell Sci. 113:3649–3662

    PubMed  CAS  Google Scholar 

  46. Landsberg J.W., Yuan J.X. 2004. Calcium and TRP channels in pulmonary vascular smooth muscle cell proliferation. News Physiol. Sci. 19:44–50

    PubMed  CAS  Google Scholar 

  47. Lang F., Busch G.L., Ritter M., Volkl H., Waldegger S., Gulbins E., Haussinger D. 1998. Functional significance of cell volume regulatory mechanisms. Physiol. Rev. 78:247–306

    PubMed  CAS  Google Scholar 

  48. Lang F., Busch G.L., Volkl H. 1998. The diversity of volume regulatory mechanisms. Cell. Physiol. Biochem. 8:1–45

    PubMed  CAS  Article  Google Scholar 

  49. Lang F., Ritter M., Gamper N., Huber S., Fillon S., Tanneur V., Lepple-Wienhues A., Szabo I., Gulbins E. 2000. Cell volume in the regulation of cell proliferation and apoptotic cell death. Cell. Physiol. Biochem. 10:417–428

    PubMed  CAS  Article  Google Scholar 

  50. Lawitts J.A., Biggers J.D. 1992. Joint effects of sodium chloride, glutamine, and glucose in mouse preimplantation embryo culture media. Mol. Reprod. Dev. 31:189–194

    PubMed  CAS  Article  Google Scholar 

  51. Lehoux S., Abe J., Florian J.A., Berk B.C. 2001. 14-3-3 Binding to Na+/H+ exchanger isoform-1 is associated with serum-dependent activation of Na+/H+ exchange. J Biol Chem 276:15794–15800

    PubMed  CAS  Article  Google Scholar 

  52. Lepple-Wienhues A., Berweck S., Bohmig M., Leo C.P., Meyling B., Garbe C., Wiederholt M. 1996. K+ channels and the intracellular calcium signal in human melanoma cell proliferation. J. Membrane Biol. 151:149–157

    CAS  Article  Google Scholar 

  53. Lipp P., Laine M., Tovey S.C., Burrell K.M., Berridge M.J., Li W., Bootman M.D. 2000. Functional InsP3 receptors that may modulate excitation-contraction coupling in the heart. Curr. Biol. 10:939–942

    PubMed  CAS  Article  Google Scholar 

  54. Lipskaia L., Lompre A.M. 2004. Alteration in temporal kinetics of Ca2+ signaling and control of growth and proliferation. Biol. Cell. 96:55–68

    PubMed  CAS  Article  Google Scholar 

  55. Madshus I.H. 1988. Regulation of intracellular pH in eukaryotic cells. Biochem. J. 250:1–8

    PubMed  CAS  Google Scholar 

  56. McLean L.A., Roscoe J., Jorgensen N.K., Gorin F.A., Cala P.M. 2000. Malignant gliomas display altered pH regulation by NHE1 compared with nontransformed astrocytes. Am. J. Physiol. 278:C676–C688

    CAS  Google Scholar 

  57. McSwine R.L., Li J., Villereal M.L. 1996. Examination of the role for Ca2+ in regulation and phosphorylation of the Na+/H+ antiporter NHE1 via mitogen and hypertonic stimulation. J. Cell Physiol. 168:8–17

    PubMed  CAS  Article  Google Scholar 

  58. Mignen O., Shuttleworth T.J. 2000. IARC, a novel arachidonate-regulated, noncapacitative Ca2+ entry channel. J. Biol. Chem. 275:9114–9119

    PubMed  CAS  Article  Google Scholar 

  59. Minke B., Cook B. 2002. TRP channel proteins and signal transduction. Physiol. Rev. 82:429–472

    PubMed  CAS  Google Scholar 

  60. Minton A.P. 2001. The influence of macromolecular crowding and macromolecular confinement on biochemical reactions in physiological media. J. Biol. Chem. 276:10577–10580

    PubMed  CAS  Article  Google Scholar 

  61. Miyake M., Kurihara K. 1983. Resting potential of the mouse neuroblastoma cells. II. Significant contribution of the surface potential to the resting potential of the cells under physiological conditions. Biochim. Biophys. Acta 762:248–255

    PubMed  CAS  Article  Google Scholar 

  62. Moneer Z., Dyer J.L., Taylor C. 2003. Nitric oxide co-ordinates the activities of the capacitative and non-capacitative Ca2+-entry pathways regulated by vasopressin. Biochem. J. 370:439–448

    PubMed  CAS  Article  Google Scholar 

  63. Montell C. 2003. The venerable inveterate invertebrate TRP channels. Cell Calcium 33:409–417

    PubMed  CAS  ISI  Article  Google Scholar 

  64. Montell C., Rubin G.M. 1989. Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction. Neuron 2:1313–1323

    PubMed  CAS  ISI  Article  Google Scholar 

  65. Munaron L. 2002. Calcium signalling and control of cell proliferation by tyrosine kinase receptors (Review). Int. J. Mol. Med. 10:671–676

    PubMed  CAS  Google Scholar 

  66. Munaron L., Antoniotti S., Lovisolo D. 2004. Intracellular calcium signals and control of cell proliferation: how many mechanisms? J. Cell. Mol. Med. 8:161–168

    PubMed  CAS  Article  Google Scholar 

  67. Nelson M.T., Patlak J.B., Worley J.F., Standen N.B. 1990. Calcium channels, potassium channels, and voltage dependence of arterial smooth muscle tone. Am. J. Physiol. 259:C3–C18

    PubMed  CAS  Google Scholar 

  68. Neufeld T.P., Edgar B.A. 1998. Connections between growth and the cell cycle. Curr. Opin. Cell Biol. 10:784–790

    PubMed  CAS  Article  Google Scholar 

  69. Nie D., Tang K., Diglio C., Honn K. V. 2000. Eicosanoid regulation of angiogenesis: role of endothelial arachidonate 12-lipoxygenase. Hem. Thromb. Vasc. Biol. 95:2304–2311

    CAS  Google Scholar 

  70. Niggli E. 1999. Localized intracellular calcium signaling in muscle: calcium sparks and calcium quarks. Annu. Rev. Physiol. 61:311–335

    PubMed  CAS  Article  Google Scholar 

  71. Nilius B., Eggermont J., Voets T., Buyse G., Manolopoulos V., Droogmans G. 1997. Properties of volume-regulated anion channels in mammalian cells. Prog. Biophys. Mol. Biol. 68:69–119

    PubMed  CAS  Article  Google Scholar 

  72. Nilius B., Wohlrab W. 1992. Potassium channels and regulation of proliferation of human melanoma cells. J. Physiol. 445:537–548

    PubMed  CAS  Google Scholar 

  73. Ouadid-Ahidouch H., Roudbaraki M., Delcourt P., Ahidouch A., Joury N., Prevarskaya N. 2004. Functional and molecular identification of intermediate-conductance Ca2+-activated K+ channels in breast cancer cells: association with cell cycle progression. Am. J. Physiol. 287:C125–C134

    CAS  Article  Google Scholar 

  74. Panet R., Atlan H. 1991. Stimulation of bumetanide-sensitive Na+/K+/Cl− cotransport by different mitogens in synchronized human skin fibroblasts is essential for cell proliferation. J. Cell Biol. 114:337–342

    PubMed  CAS  Article  Google Scholar 

  75. Panet R., Markus M., Atlan H. 1994. Bumetanide and furosemide inhibited vascular endothelial cell proliferation. J. Cell Physiol. 158:121–127

    PubMed  CAS  Article  Google Scholar 

  76. Pappas C.A., Ullrich N., Sontheimer H. 1994. Reduction of glial proliferation by K+ channel blockers is mediated by changes in pHi. NeuroReport 6:193–196

    PubMed  CAS  ISI  Google Scholar 

  77. Pardo L.A., del Camino D., Sanchez A., Alves F., Bruggemann A., Beckh S., Stuhmer W. 1999. Oncogenic potential of EAG K+ channels. EMBO J. 18:5540–5547

    PubMed  CAS  ISI  Article  Google Scholar 

  78. Parekh A.B., Tenner R. 1997. Store depletion and calcium influx. Physiol. Rev. 77:901–930

    PubMed  CAS  Google Scholar 

  79. Parekh A.B., Putney JR, J.W. 2005. Store-operated calcium channels. Physiol. Rev. 85:757–810

    PubMed  CAS  Article  Google Scholar 

  80. Paris S., Pouyssegur J. 1986. Growth factors activate the bumetanide-sensitive Na+/K+/Cl-cotransport in hamster fibroblasts. J. Biol. Chem. 261:6177–6183

    PubMed  CAS  Google Scholar 

  81. Parsegian V.A., Rand R.P., Rau D.C. 2000. Osmotic stress, crowding, preferential hydration, and binding: A comparison of perspectives. Proc. Natl. Acad. Sci. USA 97:3987–3992

    PubMed  CAS  Article  Google Scholar 

  82. Petronini P.G., De Angelis E.M., Borghetti P., Borghetti A.F., Wheeler K.P. 1992. Modulation by betaine of cellular responses to osmotic stress. Biochem. J. 282:69–73

    PubMed  CAS  Google Scholar 

  83. Platoshyn O., Golovina V.A., Bailey C.L., Limsuwan A., Krick S., Juhaszova M., Seiden J.E., Rubin L.J., Yuan J.X. 2000. Sustained membrane depolarization and pulmonary artery smooth muscle cell proliferation. Am. J. Physiol. 279:C1540–C1549

    CAS  Google Scholar 

  84. Polymenis M., Schmidt E.V. 1999. Coordination of cell growth with cell division. Curr. Opin. Genet. Dev. 9:76–80

    PubMed  CAS  Article  Google Scholar 

  85. Reshkin S.J., Bellizzi A., Caldeira S., Albarani V., Malanchi I., Poignee M., Alunni-Fabbroni M., Casavola V., Tommasino M. 2000. Na+/H+ exchanger-dependent intracellular alkalinization is an early event in malignant transformation and plays an essential role in the development of subsequent transformation-associated phenotypes. FASEB J. 14:2185–2197

    PubMed  CAS  ISI  Article  Google Scholar 

  86. Robbins E., Pederson T., Klein P. 1970. Comparison of mitotic phenomena and effects induced by hypertonic solutions in HeLa cells. J. Cell Biol. 44:400–416

    PubMed  CAS  Article  Google Scholar 

  87. Rotin D., Steele-Norwood D., Grinstein S., Tannock I. 1989. Requirement of the Na+/H+ exchanger for tumor growth. Cancer Res. 49:205–211

    PubMed  CAS  ISI  Google Scholar 

  88. Rouzaire-Dubois B., Dubois J.M. 1991. A quantitative analysis of the role of K+ channels in mitogenesis of neuroblastoma cells. Cell. Signal. 3:333–339

    PubMed  CAS  Article  Google Scholar 

  89. Rouzaire-Dubois B., Dubois J.M. 1998. K+ channel block-induced mammalian neuroblastoma cell swelling: a possible mechanism to influence proliferation. J. Physiol. 510:93–102

    PubMed  CAS  Article  Google Scholar 

  90. Santella L. 1998. The role of calcium in the cell cycle: facts and hypotheses. Biochem. Biophys. Res. Commun. 244:317–324

    PubMed  CAS  Article  Google Scholar 

  91. Schlessinger J. 2000. Cell signaling by receptor tyrosine kinases. Cell 103:211–225

    PubMed  CAS  ISI  Article  Google Scholar 

  92. Schliess F., Schreiber R., Häussinger D. 1995. Activation of extracellular signal-regulated kinases Erk-1 and Erk-2 by cell swelling in H4IIE hepatoma cells. Biochem. J. 309:13–17

    PubMed  CAS  Google Scholar 

  93. Sham J.S., Cleemann L., Morad M. 1992. Gating of the cardiac Ca2+ release channel: the role of Na+ current and Na+-Ca2+ exchange. Science 255:850–853

    PubMed  CAS  ISI  Article  Google Scholar 

  94. Short A.D., Bian J., Ghosh T.K., Waldron R.T., Rybak S.L., Gill D.L. 1993. Intracellular Ca2+ pool content is linked to control of cell growth. Proc. Natl. Acad. Sci. USA 90:4986–4990

    PubMed  CAS  Article  Google Scholar 

  95. Shrode L.D., Tapper H., Grinstein S. 1997. Role of intracellular pH in proliferation, transformation, and apoptosis. J. Bioenerg. Biomembr. 29:393–399

    PubMed  CAS  Article  Google Scholar 

  96. Shuttleworth T.J., Mignen O. 2003. Calcium entry and the control of calcium oscillations. Biochem. Soc. Trans. 31:916–919

    PubMed  CAS  Article  Google Scholar 

  97. Spassova M.A., Soboloff J., He L.P., Hewavitharana T., Xu W., Venkatachalam K., van Rossum D.B., Patterson R.L., Gill D.L. 2004. Calcium entry mediated by SOCs and TRP channels: variations and enigma. Biochim. Biophys. Acta. 1742:9–20

    PubMed  CAS  Article  Google Scholar 

  98. Stubbs M., Veech R.L., Griffiths J.R. 1995. Tumor metabolism: the lessons of magnetic resonance spectroscopy. Adv. Enzyme Regul. 35:101–115

    PubMed  CAS  Article  Google Scholar 

  99. Sweeney M., McDaniel S.S., Platoshyn O., Zhang S., Yu Y., Lapp B.R., Zhao Y., Thistlethwaite P.A., Yuan J.X. 2005. Role of capacitative Ca2+ entry in bronchial contraction and remodeling. J. Appl. Physiol. 92:1594–1602

    Google Scholar 

  100. Tominaga T., Barber D.L. 1998. Na-H exchange acts downstream of RhoA to regulate integrin-induced cell adhesion and spreading. Mol. Biol. Cell. 9:2287–2303

    PubMed  CAS  Google Scholar 

  101. Tominaga T., Ishizaki T., Narumiya S., Barber D.L. 1998. P160ROCK mediates RhoA activation of Na-H exchange. EMBO J. 17:4712–4722

    PubMed  CAS  ISI  Article  Google Scholar 

  102. Trepakova E.S., Gericke M., Hirakawa Y., Weisbrod R.M., Cohen R.A., Bolotina V.M. 2001. Properties of a native cation channel activated by Ca2+ store depletion in vascular smooth muscle cells. J. Biol. Chem. 276:7782–7790

    PubMed  CAS  Article  Google Scholar 

  103. Tsien R.W., Tsien R.Y. 1990. Calcium channels, stores, and oscillations. Annu. Rev. Cell Biol. 6:715–760

    PubMed  CAS  Article  Google Scholar 

  104. Vanden Abeele F., Shuba Y., Roudbaraki M., Lemonnier L., Vanoverberghe K., Mariot P., Skryma R., Prevarskaya N. 2003. Store-operated Ca2+ channels in prostate cancer epithelial cells: function, regulation, and role in carcinogenesis. Cell Calcium 33:357–373

    PubMed  CAS  ISI  Article  Google Scholar 

  105. Vaupel P., Kallinowski F., Okunieff P. 1989. Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res. 49:6449–6465

    PubMed  CAS  ISI  Google Scholar 

  106. Vicentini L.M., Villereal M.L. 1986. Inositol phosphates turnover, cytosolic Ca2+ and pH: putative signals for the control of cell growth. Life Sci. 38:2269–2276

    PubMed  CAS  ISI  Article  Google Scholar 

  107. Wakabayashi S., Shigekawa M., Pouyssegur J. 1997. Molecular physiology of vertebrate Na+/H+ exchangers. Physiol. Rev. 77:51–74

    PubMed  CAS  Google Scholar 

  108. Wang Z. 2004. Roles of K+ channels in regulating tumour cell proliferation and apoptosis. Pflügers Arch. 448:274–286

    PubMed  CAS  Article  Google Scholar 

  109. Warmke J., Drysdale R., Ganetzky B. 1991. A distinct potassium channel polypeptide encoded by the Drosophila eag locus. Science 252:1560–1562

    PubMed  CAS  ISI  Article  Google Scholar 

  110. Watson E.L., Jacobson K.L., Singh J.C., DiJulio D.H. 2004. Arachidonic acid regulates two Ca2+ entry pathways via nitic oxide. Cell Signal 16:157–165

    PubMed  CAS  Article  Google Scholar 

  111. Whatley R.E., Satoh K., Zimmermann G.A., McIntyre T.M., Prescott S.M. 1994. Proliferation-dependent changes in release of arachidonic acid from endothelial cells. J. Clin. Invest. 94:1889–1900

    PubMed  CAS  Article  Google Scholar 

  112. Whitfield J.F. 1992. Calcium signals and cancer. Crit. Rev. Oncog. 3:55–90

    PubMed  CAS  Google Scholar 

  113. Whitfield J.F. 1995 Calcium in Cell Cycles and Cancer. 2nd ed., CRC Press, Boca Raton, New York, London, Tokyo

    Google Scholar 

  114. Whitfield J.F., Boynton A.L., MacManus J.P., Sikorska M., Tsang B.K. 1979. The regulation of cell proliferation by calcium and cyclic AMP. Mol. Cell. Biochem. 27:155–179

    PubMed  CAS  Article  Google Scholar 

  115. Wike-Hooley J.L., Haveman J., Reinhold H.S. 1984. The relevance of tumour pH to the treatment of malignant disease. Radiother Oncol. 2:343–366

    PubMed  CAS  Article  Google Scholar 

  116. Wilson G.F., Chiu S.Y. 1993. Mitogenic factors regulate ion channels in Schwann cells cultured from newborn rat sciatic nerve. J. Physiol. 470:501–520

    PubMed  CAS  Google Scholar 

  117. Wondergem R., Gong W., Monen S.H., Dooley S.N., Gonce J.L., Conner T.D., Houser M., Ecay T.W., Ferslew K.E. 2001. Blocking swelling-activated chloride current inhibits mouse liver cell proliferation. J. Physiol. 532:661–672

    PubMed  CAS  Article  Google Scholar 

  118. Wu X., Babnigg G., Zagranichnaya T., Villereal M.L. 2002. The role of endogenous human Trp4 in regulating carbachol-induced calcium oscillations in HEK-293 cells. J. Biol. Chem. 277:13597–13608

    PubMed  CAS  Article  Google Scholar 

  119. Yancey P.H., Burg M.B. 1990. Counteracting effects of urea and betaine in mammalian cells in culture. Am. J. Physiol. 258:R198–R204

    PubMed  CAS  Google Scholar 

  120. Yancey P.H., Burg M.B., Bagnasco S.M. 1990. Effects of NaCl, glucose, and aldose reductase inhibitors on cloning efficiency of renal medullary cells. Am. J. Physiol. 258:C156–C163

    PubMed  CAS  Google Scholar 

  121. Yu Y., Sweeney M., Zhang S., Platoshyn O., Landsberg J., Rothman A., Yuan J.X. 2003. PDGF stimulates pulmonary vascular smooth muscle cell proliferation by upregulating TRPC6 expression. Am. J. Physiol. 284:C316–C330

    CAS  Google Scholar 

  122. Yuan X.J. 1995. Voltage-gated K+ currents regulate resting membrane potential and [Ca2+]i in pulmonary arterial myocytes. Circ. Res. 77:370–378

    PubMed  CAS  Google Scholar 

  123. Zachos N.C., Tse M., Donowitz M. 2005. Molecular physiology of intestinal Na+/H+ exchange. Annu. Rev. Physiol. 67:411–443

    PubMed  CAS  Article  Google Scholar 

Download references

Acknowledgement

I thank Prof. Karl Kunzelmann for valuable discussions and critical reading of the manuscript. This article was supported by DFG SCHR752/2-1.

Author information

Affiliations

  1. Institut für Physiologie, Universität Regensburg, Universitätsstr. 31, Regensburg, D-93053, Germany

    R. Schreiber

Authors
  1. R. Schreiber
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R. Schreiber.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Schreiber, R. Ca2+ Signaling, Intracellular pH and Cell Volume in Cell Proliferation. J Membrane Biol 205, 129 (2005). https://doi.org/10.1007/s00232-005-0778-z

Download citation

  • Received:

  • DOI: https://doi.org/10.1007/s00232-005-0778-z

Keywords

  • Cell proliferation
  • Tumor growth
  • Intracellular calcium
  • Calcium signalling
  • Calcium entry
  • TRP-Channels
  • Intracellular pH
  • pH homeostasis
  • Sodium-proton exchanger
  • Cell volume