Skip to main content
SpringerLink
Log in

Intracellular Monovalent Ions as Second Messengers

  • Topical Review
  • Published:
The Journal of Membrane Biology Aims and scope Submit manuscript

Abstract

It is generally accepted that electrochemical gradients of monovalent ions across the plasma membrane, created by the coupled function of pumps, carriers and channels, are involved in the maintenance of resting and action membrane potential, cell volume adjustment, intracellular Ca2+ handling and accumulation of glucose, amino acids, nucleotides and other precursors of macromolecular synthesis. In the present review, we summarize data showing that side-by-side with these classic functions, modulation of the intracellular concentration of monovalent ions in a physiologically reasonable range is sufficient to trigger numerous cellular responses, including changes in enzyme activity, gene expression, protein synthesis, cell proliferation and death. Importantly, the engagement of monovalent ions in regulation of the above-listed cellular responses occurs at steps upstream of Ca2+ i and other key intermediates of intracellular signaling, which allows them to be considered as second messengers. With the exception of HCO −3 -sensitive soluble adenylyl cyclase, the molecular origin of sensors involved in the function of monovalent ions as second messengers remains unknown.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Adragna N., Di Fulvio M., Lauf P.K. 2004. Regulation of K-Cl cotransport: from function to genes. J. Membane. Biol. 201:109–137

    Article  CAS  Google Scholar 

  2. Akar F., Jiang G., Paul R.J., O’Neill W.C. 2001. Contractile regulation of the Na+-K+-2Cl− cotransporter in vascular smooth muscle. Am. J. Physiol. 281:C579–C584

    CAS  Google Scholar 

  3. Akar F., Skinner E., Klein J.D., Jena M., Paul R.J., O’Neill W.C. 1999. Vasoconstrictors and nitrovasodilators reciprocally regulate the Na+-K+-2Cl− cotransporter in rat aorta. Am. J. Physiol. 276:C1383–C1390

    PubMed  CAS  Google Scholar 

  4. Akimova O.A., Bagrov A.Y., Lopina O.D., Kamernitsky A.V., Tremblay J., Hamet P., Orlov S.N. 2005.Cardiotonic steroids differentially affect intracellular Na+ and [Na+]i/[K+]i-independent signaling in C7-MDCK cells. J. Biol. Chem. 280:832–839

    PubMed  CAS  Google Scholar 

  5. Akimova O.A., Pchejetski D., Hamet P., Orlov S.N. 2006. Modest intracellular acidification suppresses death signaling in ouabain-treated cells. Pfluegers Archiv 451:569–578

    Article  PubMed  CAS  Google Scholar 

  6. Al-Habori M. 2001. Macromolecular crowding and its role as intracellular signalling of cell volume regulation. Int. J. Biochem. Cell Biol. 33:844–864

    Article  PubMed  CAS  Google Scholar 

  7. Anfinogenova Y.J., Baskakov M.B., Kovalev I.V., Kilin A.A., Dulin N.O., Orlov S.N. 2004. Cell-volume-dependent vascular smooth muscle contraction: role of Na+, K+, 2Cl− cotransport, intracellular Cl− and L-type Ca2+ channels. Pfluegers Archiv 449:42–55

    Article  PubMed  CAS  Google Scholar 

  8. Barone F.C., White R.F., Spera P.A., Ellison J., Currie R. W., Wang X., Feuerstein G. Z. 1998. Ischemic preconditioning and brain tolerance. Temporal histological and functional outcomes, protein synthesis requirement, and interleukin-1 receptor antagonists and early gene expression. Stroke 29:1937–1951

    PubMed  CAS  Google Scholar 

  9. Bennekou P., Christophersen. P. 2003. Ion channels. In:. Bernhardt I., Ellory J. C., eds. Red Cell Membrane Transport in Health and Disease. Springer, Berlin pp 139–152.

    Google Scholar 

  10. Berridge M.J. 1993. Inositol triphosphate and calcium signalling. Nature 361:315–325

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  12. Blumenstein Y., Maximyuk O.P., Lozovaya N., Yatsenko N.M., Kanevsky N., Kristal O., Dascal N. 2004. Intracellular Na+ inhibits voltage-dependent N-type Ca2+ channels by a G protein βγ subunit-dependent mechanism. J. Physiol. 556:121–134

    Article  PubMed  CAS  Google Scholar 

  13. Breitwieser G.E., Altamirano A.A., Russell J.M. 1990. Osmotic stimulation of Na+-K+-Cl− cotransport in squid giant axon is [Cl−]i dependent. Am. J. Physiol. 258:C749–C753

    PubMed  CAS  Google Scholar 

  14. Brown R.A., Chipperfield A.R., Davis J.P.L., Harper A.A. 1999. Increased (Na+K+Cl−) cotransport in rat arterial smooth muscle in deoxycorticosterone (DOCA)/salt-induced hypertension. J. Vasc. Res. 36:492–501

    Article  PubMed  CAS  Google Scholar 

  15. Burns C.P., Rozengurt E. 1984. Extracellular Na+ and initiation of DNA synthesis: role of intracellular pH and K+. J. Cell Biol. 98:1082–1089

    Article  PubMed  CAS  Google Scholar 

  16. Cahn F., Lubin M. 1978. Inhibition of elongation steps of protein synthesis at reduced potassium concentrations in reticulocytes, reticulocyte lysate. J. Biol. Chem. 253:7798–7803

    PubMed  CAS  Google Scholar 

  17. Canessa M., Salazar G., Werner E., Vallega G., Gonzalez A. 1994. Cell growth and Na-K-Cl cotransport responses of vascular smooth muscle cells of Milan rats. Hypertension 23:1022–1026

    PubMed  CAS  Google Scholar 

  18. Carafoli E. 2002. Calcium signaling: a tale for all seasons. Proc. Natl. Acad. Sci. USA 99:1115–1122

    Article  PubMed  CAS  Google Scholar 

  19. Chen Y., Cann M.J., Litvin T.N., Iourgenko V., Sinclair M.L., Levin L.R., Buck J. 2000. Soluble adenylyl cyclase as an evolutionarily conserved bicarbonate sensor. Science 289:625–628

    Article  PubMed  CAS  Google Scholar 

  20. Cheng H.F., Wang J.L., Zhang M.Z., McKanna J.A.M., Harris. R.C. 2000. Role of p38 in the regulation of renal cortical cyclooxygenase-2 expression by extracellular chloride. J. Clin. Invest. 106:681–688

    PubMed  CAS  Google Scholar 

  21. Chipperfield A.R., Harper A.A. 2001. Chloride in smooth muscle. Prog. Biophys. Mol. Biol. 74:175–221

    Article  Google Scholar 

  22. Contreras R.G., Lazaro A., Mujica A., Gonzalez-Mariscal L., Valdes J., Garcia-Villegas M. R., Cereijido M. 1995. Ouabain resistance of the epithelial cell line (Ma104) is not due to lack of affinity of its pumps for the drug. J. Membrane Biol. 145:295–300

    CAS  Google Scholar 

  23. Contreras R. G., Shoshani L., Flores-Maldonado C., Lazaro A., Cereijido M. 1999. Relationship between Na+, K+-ATPase and cell attachment. J. Cell Sci. 112:4223–4232

    PubMed  CAS  Google Scholar 

  24. Coulon V., Veyrune J.-L., Tourkine N., Vié A., Hipskind R.A., Blanchard J.-M. 1999. A novel calcium signaling pathway targets the c-fos intragenic transcriptional pausing site. J. Biol. Chem. 274:30439–30446

    Article  PubMed  CAS  Google Scholar 

  25. Cutaia M., Tollefson K., Kroczynski J., Parks N., Rounds S. 2000. Role of Na/H antiport in pH-dependent cell death in pulmonary artery endothelial cells. Am. J. Physiol. 278:L536–L544

    CAS  Google Scholar 

  26. D’Arcangelo D., Facchiano F., Barlucchi L.M., Melilo G., Illi B., Testolin L., Gaetano, C. et al. 2000.Acidosis inhibits endothelial cell apoptosis and function and induces basic fibroblast growth factor and vascular endothelial growth factor expression. Circ. Res. 86:312–318

    PubMed  CAS  Google Scholar 

  27. D’Arcangelo D., Gaetano C., Capogrossi M.C. 2002. Acidification prevents endothelial cell apoptosis by Axl activation. Circ. Res. 91:e4–e12

    Article  PubMed  Google Scholar 

  28. Davis J.P.L., Chipperfield A.R., Harper A.A. 1993. Accumulation of intracellular chloride by (Na-K-Cl) cotransport in rat arterial smooth muscle is enhanced in deoxycorticosterone acetate (DOCA)/salt hypertension. J. Mol. Cell. Cardiol. 25:233–237

    Article  PubMed  CAS  Google Scholar 

  29. Delpire E. 2000. Cation-chloride cotransporters in neuronal communication. News Physiol. Sci. 15:309–312

    PubMed  CAS  Google Scholar 

  30. Dorovkov M.V., Pavur K.S., Petrov A.N., Ryazanov A.G. 2002. Regulation of elongation factor-2 kinase by pH. Biochemistry 41:13444–13450

    Article  PubMed  CAS  Google Scholar 

  31. Ewart H.S., Klip A. 1995. Hormonal regulation of the Na+-K+-ATPase: mechanisms underlying rapid and sustained changes in pump activity. Am. J. Physiol. 269:C295–C311

    PubMed  CAS  Google Scholar 

  32. Falciola J., Volet B., Anner R. M., Moosmayer M., Lacotte D., Anner B.M. 1994. Role of cell membrane Na, K-ATPase for survival of human lymphocytes in vivo. Biosci. Rep. 14:189–204

    Article  PubMed  CAS  Google Scholar 

  33. Féraille E., Doucet A. 2001. Sodium-potassium-adenosinetriphosphatase-dependent sodium transport in the kidney: hormonal control. Physiol. Rev. 81:345–418

    PubMed  Google Scholar 

  34. Folkow B. 1982. Physiological aspects of primary hypertension. Physiol. Rev. 62:347–504

    PubMed  CAS  Google Scholar 

  35. Francisco L.J., Osborn J.L., DiBona G.F. 1982. Prostaglandins in renin release during sodium deprivation. Am. J. Physiol. 243:F261–F268

    Google Scholar 

  36. Gagnon F., Hamet P., Orlov S.N. 1999. Na+, K+ pump and Na+-coupled ion carriers in isolated mammalian kidney epithelial cells: regulation by protein kinase C. Can. J. Physiol. Pharmacol. 77:305–319

    Article  PubMed  CAS  Google Scholar 

  37. Garty N.B., Salomon Y. 1987.Stimulation of partially purified adenylate cyclase from bull sperm by bicarbonate. FEBS Lett 218:148–152

    Article  PubMed  CAS  Google Scholar 

  38. Grinstein S., Furuya W., Downey G.P. 1992. Activation of permeabilized neutrophils: role of anions. Am. J. Physiol. 263:C78–C85

    PubMed  CAS  Google Scholar 

  39. Grinstein S., Smith J.D., Benedict S.H., Gelfand E.W. 1989. Activation of sodium-hydrogen exchange by mitogens. Curr. Topics Membr. Transport 34:331–343

    Google Scholar 

  40. Guyton A.C. 1980. Arterial Pressure and Hypertension. WB Saunders, Philadelphia

    Google Scholar 

  41. Guyton A.C., Coleman T.G., Cowley A.W. Jr., Scheel K.W., Manning R.D. Jr., Norman R.A. Jr. 1975. Arterial pressure regulation: overriding dominance of the kidney in long-term regulation and in hypertension. In: Laragh J.H., ed. Hypertension Mechanisms. York Medical Books, New York, pp 1–24

    Google Scholar 

  42. Haas M., McBrayer D., Lytle C. 1995. [Cl−]i-dependent phosphorylation of the Na-K-Cl cotransport protein of dog tracheal epithelial cells. J. Biol. Chem. 270:28955–2861

    Article  PubMed  CAS  Google Scholar 

  43. Hadrava V., Tremblay J., Sekaly R.-P., Hamet P. 1992. Accelerated entry of smooth muscle cells from spontaneously hypertensive rats into the S phase of the cell cycle. Biochem. Cell Biol. 70:599–604

    Article  PubMed  CAS  Google Scholar 

  44. Hamet P., Orlov S.N., DeBlois D., Sun Y., Kren V., Tremblay J. 2004. Angiotensin as a cytokine implicated in accelerated cellular turnover. In: Unger T., Scholkens B.A. eds. Handbook of Experimental Pharmacology. Unger, Springer Verlag, New York, pp 71–98

    Google Scholar 

  45. Hayashi H., Szaszi K., Grinstein S. 2002. Multiple modes of regulation of Na+/H+ exchangers. Ann. N.Y. Acad. Sci. 976:248–258

    Article  PubMed  CAS  Google Scholar 

  46. He X.R., Greenberg S.C., Briggs J.P., Schermann J. 2005.Effects of furosemide and verapamil on the NaCl dependency of macula densa-mediated renin secretion. Hypertension 26:137–142

    Google Scholar 

  47. Heizmann C. W., Hunziker W. 1991. Intracellular calcium-binding proteins: more sites than insights. TiBS 16:98–103

    PubMed  CAS  Google Scholar 

  48. Herrera R.E., Nordheim A., Stewart A.F. 1997. Chromatin structure analysis of the human c-Fos promoter rveals a centrally positioned nucleosome. Chromosoma 106:284–292

    Article  PubMed  CAS  Google Scholar 

  49. Isaev N.K., Stelmashook E.V., Halle A., Harms C., Lautenschlager M., Weih M., Dirnagl, U. et al. 2000. Inhibition of Na+, K+-ATPase activity in cultured cerebellar granule cells prevents the onset of apoptosis induced by low potassium. Neurosci. Lett. 283:41–44

    Article  PubMed  CAS  Google Scholar 

  50. Islam C.F., Mathie R.T., Dinneen M.D., Kiely E.A., Peters A.M., Grace P.A. 1997. Ischemia-reperfusion injury in the rat kidney: the effect of preconditioning. Br. J. Urol. 79:842–847

    PubMed  CAS  Google Scholar 

  51. Iwamoto L.M., Fujiwara N., Nakamura K.T., Wada R.K. 2004. Na-K-2Cl cotransporter inhibition impairs human lung cellular proliferation. Am. J. Physiol. 287:L510–L514

    CAS  Google Scholar 

  52. Jiang G., Klein J.D., O’Neill W.C. 2001. Growth factors stimulate the Na-K-2Cl cotransporter NKCC1 through a novel Cl−-dependent mechanism. Am. J. Physiol. 281:C1948–C1953

    CAS  Google Scholar 

  53. Kotchen T.A. 2005. Contribution of sodium and chloride to NaCl-induced hypertension. Hypertension 45:849–850

    Article  PubMed  CAS  Google Scholar 

  54. Kotchen T.A., Galla J. H., Luke R.G. 1976. Failure of NaHCO3 and KHCO3 to inhibit renin in the rat. Am. J. Physiol. 231:F1050–F1056

    Google Scholar 

  55. Kovalev I.V., Baskakov M.B., Anfinogenova Y.J., Borodin Y.L., Kilin A.A., Minochenko I.L., Popov, A.G. et al. 2003. Effect of Na+, K+, 2Cl− cotransport inhibitor bumetanide on electrical and contractile activity of smooth muscle cells in guinea pig ureter. Bull. Exp. Biol. Med. 136(8):145–149

    Article  PubMed  CAS  Google Scholar 

  56. Kuchler R.J. 1967. The role of sodium and potassium in regulating amino acid accumulation and protein synthesis in LM-strain mouse fibroblasts. Biochim. Biophys. Acta 136:473–483

    PubMed  CAS  Google Scholar 

  57. Laamarti M.A., Bell P.D., Lapointe J.-Y. 1998. Transport and regulatory properties of the apical Na-K-2Cl cotransporter of macula densa cells. Am. J. Physiol. 275:F703–F709

    PubMed  CAS  Google Scholar 

  58. Lanius R.A., Pasqualotto B.A., Shaw C.A. 1993. γ-Aminobutyric acid A receptor regulation by a chloride-dependent kinase and a sodium-dependent phosphatase. Brain Res. Mol. Brain Res. 20:192–198

    Article  PubMed  CAS  Google Scholar 

  59. Ledbetter M.L.S., Lubin M. 1977. Control of protein synthesis in human fibroblasts by intracellular potassium. Exp. Cell Res. 105:223–236

    Article  PubMed  CAS  Google Scholar 

  60. Lee J.-M., Grabb M.C., Zipfel G.J., Choi D. W. 2000. Brain tissue responses to ischemia. J. Clin. Invest. 106:723–731

    PubMed  CAS  Google Scholar 

  61. Lenart B., Kintner D.B., Shull G.E., Sun D. 2004. Na-K-Cl cotransporter-mediated intracellular Na+ accumulation affects Ca2+ signaling in astrocytes in an in vitro ischemic model. J. Neurosci. 24:9585–9597

    Article  PubMed  CAS  Google Scholar 

  62. Li Y.W., Whittaker P., Kloner R.A. 1992. The transient nature of the effect of ischemic preconditioning on myocardial infarct size and ventricular arrhythmia. Am. Heart J. 123:346–353

    Article  PubMed  CAS  Google Scholar 

  63. Lincoln T.M., Cornwell T. L. 1993. Intracellular cyclic GMP receptor proteins. FASEB J. 7:328–338

    PubMed  CAS  Google Scholar 

  64. Lubin M. 1967. Intracellular potassium and macromolecular synthesis in mammalian cells. Nature 213:451–453

    Article  PubMed  CAS  Google Scholar 

  65. Lubin M., Ennis H.L. 1964. On the role of intracellular potassium in protein synthesis. Biochim. Biophys. Acta 80:614–631

    PubMed  CAS  Google Scholar 

  66. Lytle C., Forbush B. 1996. Regulatory phosphorylation of the secretory Na-K-Cl cotransporter: modulation by cytoplasmic Cl. Am. J. Physiol. 270:C437–C448

    PubMed  CAS  Google Scholar 

  67. Maingret F., Patel A., Lesage J.F., Lazdunski M., Honoré. E. 1999. Mechano- and acid stimulation, two interactive modes of activation of the TREK-1 potassium channels. J. Biol. Chem. 274:26691–26696

    Article  PubMed  CAS  Google Scholar 

  68. Majno G., Joris. I. 1995. Apoptosis, oncosis, and necrosis. An overview of cell death. Am. J. Pathol. 146:3–15

    PubMed  CAS  Google Scholar 

  69. Mallis L., Guber H., Adler S.G., Palant C.E. 1991. Intracellular chloride activity in cultured mesangial cells. Renal Physiol. Biochem. 14:12–18

    PubMed  CAS  Google Scholar 

  70. Marakhova I.I., Vereninov A.A., Toropova F.V., Vinogradova T.A. 1998. Na,K,-ATPase pump in activated human lymphocytes: on the mechanisms of rapid and long-term increase in K influxes during the initiation of phytohemagglutinin-induced proliferation. Biochim. Biophys. Acta. 1368:61–72

    Article  PubMed  CAS  Google Scholar 

  71. Matsuyama S., Reed J.C. 2000. Mitochondria-dependent apoptosis and cellular pH regulation. Cell Death Different. 7:1155–1165

    Article  CAS  Google Scholar 

  72. Mechti N., Piechaczyk M., Blanchard J.M., Jeanteur P., Lebleu B. 1991. Sequence requirements for premature transcription arrest within the first intron of the mouse c-fos gene. Mol. Cell. Biol. 11:2832–2841

    PubMed  CAS  Google Scholar 

  73. Meeker G.L. 1970. Intracellular potassium requirement for protein synthesis and mitotic apparatus in sea urchin eggs. Exp. Cell Res. 63:165–170

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  75. Muimo R., Banner S.J., Marshall L.J., Mehta A. 1998. Nucleoside diphosphate kinase and Cl−-sensitive protein phosphorylation in apical membranes from ovine airway epithelium. Am. J. Respir. Cell Mol.Biol. 18:270–278

    PubMed  CAS  Google Scholar 

  76. Nakagawa Y., Rivera V., Larner A.C. 1992. A role for Na/K-ATPase in the control of human c-fos and c-jun transcription. J. Biol. Chem. 267:8785–8788

    PubMed  CAS  Google Scholar 

  77. O’Neill W.C., Steinberg D.F. 1995. Functional coupling of Na+-K+-2Cl− cotransport and Ca2+-dependent K+ channels in vascular endothelial cells. Am. J. Physiol 269:C267–C274

    PubMed  CAS  Google Scholar 

  78. Obermuller N., Kunchaparfy S., Ellison D.H., Bachmann S. 1996. Expression of the Na-K-2Cl cotransporter by macula densa and thick ascending limb cells of rabbit and rat nephron. J. Clin. Invest. 98:635–640

    PubMed  CAS  Google Scholar 

  79. Okamura N., Tajima Y., Onoe S., Sugita Y. 1991. Purification of bicarbonate-sensitive sperm adenylyl cyclase by 4-acetamido-4′-isothiocyanostilbene-2,2′-disulfonic acid-affinity chromatography. J. Biol. Chem. 266:17754–17759

    PubMed  CAS  Google Scholar 

  80. Orlov S.N., Adragna N., Adarichev V.A., Hamet P. 1999. Genetic and biochemical determinants of abnormal monovalent ion transport in primary hypertension. Am. J. Physiol. 276:C511–C536

    PubMed  CAS  Google Scholar 

  81. Orlov S.N., Akimova O.A., Hamet P. 2005. Cardiotonic steroids: novel mechanisms of Na+ i-mediated and -independent signaling involved in the regulation of gene expression, proliferation and cell death. Curr. Hypertens. Rev. 1:143–257

    Article  Google Scholar 

  82. Orlov S.N., Hamet P. 2004. Apoptosis vs oncosis: role of cell volume and intracellular monovalent cations. Adv. Exp. Med. Biol. 559:219–233

    Article  CAS  PubMed  Google Scholar 

  83. Orlov S.N., Resink T.J., Bernhardt J., Ferracin F., Buhler F.R. 1993. Vascular smooth muscle cell calcium transport. Regulation by angiotensin II and lipoproteins. Hypertension 21:195–203

    PubMed  CAS  Google Scholar 

  84. Orlov S.N., Taurin S., Thorin-Trescases N., Dulin N.O., Tremblay J., Hamet P. 2000. Inversion of the intracellular Na+/K+ ratio blocks apoptosis in vascular smooth muscle cells by induction of RNA synthesis. Hypertension 35:1062–1068

    PubMed  CAS  Google Scholar 

  85. Orlov S.N., Taurin S., Tremblay J., Hamet P. 2001. Inhibition of Na+, K+ pump affects nucleic acid synthesis and smooth muscle cell proliferation via elevation of the [Na+]i/[K+]i ratio: possible implication in vascular remodeling. J. Hypertens. 19:1559–1565

    Article  PubMed  CAS  Google Scholar 

  86. Orlov S.N., Thorin-Trescases N., Kotelevtsev S.V., Tremblay J., Hamet P. 1999. Inversion of the intracellular Na+/K+ ratio blocks apoptosis in vascular smooth muscle at a site upstream of caspase-3. J. Biol. Chem. 274:16545–16552

    Article  PubMed  CAS  Google Scholar 

  87. Orlov S.N., Thorin-Trescases N., Pchejetski D., Taurin S., Farhat N., Tremblay J., Thorin, E. et al. 2004. Na+/K+ pump and endothelial cell survival: [Na+]i/[K+]i-independent necrosis triggered by ouabain, and protection against apoptosis mediated by elevation of [Na+]i. Pfluegers Arch. 448:335–345

    Article  CAS  Google Scholar 

  88. Orlov S.N., Tremblay J., DeBlois D., Hamet. P. 2002. Genetics in programmed cell death and proliferation. Semin. Nephrol. 22:161–171

    Article  PubMed  CAS  Google Scholar 

  89. Orlov S.N., Tremblay J., Hamet P. 1996. Bumetanide-sensitive ion fluxes in vascular smooth muscle cells: lack of functional Na+, K+, 2Cl− cotransport. J. Membrane Biol. 153:125–135

    Article  CAS  Google Scholar 

  90. Orlowski J., Grinstein S. 2004. Diversity of the mammalian sodium/proton exchanger SLC9 gene family. Pfluegers Arch. 447:549–565

    Article  CAS  Google Scholar 

  91. 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

    Article  PubMed  CAS  Google Scholar 

  92. Panet R., Ellash M., Pick M., Atlan H. 2002. Na+/K+/Cl− cotransporter activates mitogen-activated protein kinase in fibroblasts and lymphocytes. J. Cell. Physiol. 190:227–237

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  94. Panet R., Markus M., Atlan H. 2000.Overexpression of the Na+/K+/Cl− cotransporter gene induces cell proliferation and phenotypic transformation in mouse fibroblasts. J. Cell. Physiol. 182:109–118

    Article  PubMed  CAS  Google Scholar 

  95. Pastor-Soler N., Beaulieu V., Litvin T.N., Da Silva N., Chen Y., Brown D., Buck, J. et al. 2003. Bicarbonate-regulated adenylyl cyclase (sAC) is a sensor that regulates pH-dependent V-ATPase recycling. J. Biol. Chem. 278:49523–49529

    Article  PubMed  CAS  Google Scholar 

  96. Pchejetski D., Taurin S., der Sarkissian S., Lopina O.D., Pshezhetsky A.V., Tremblay J., DeBlois, D. et al. 2003. Inhibition of Na+, K+-ATPase by ouabain triggers epithelial cell death independently of inversion of the [Na+]i/[K+]i ratio. Biochem. Biophys. Res. Commun. 301:735–744

    Article  PubMed  CAS  Google Scholar 

  97. Perez-Sala D., Collado-Escobar D., Mollinedo F. 1995. Intracellular alkalinization suppresses lovastatin-induced apoptosis in HL-60 cells through the inactivation of a pH-dependent endonuclease. J. Biol. Chem. 270:6235–6242

    Article  PubMed  CAS  Google Scholar 

  98. Pirutin S.K., Turovetsky V.B., Kudryashov Y.B., Rubin A.B. 2002. Modification of damaging effect of ultraviolet radiation on mice peritoneal macrophage membranes. Radiat. Biol. Radioecol. 42:151–154

    CAS  Google Scholar 

  99. Pollack G. H. 2004. Cells, Gels and the Engines of Life. Ebner & Sons, Seattle, WA

    Google Scholar 

  100. Pollack M., Fisher H.W. 1976. Dissociation of ribonucleic acid and protein synthesis in mammalian cells deprived of potassium. Arch. Biochem. Biophys. 172:188–190

    Article  CAS  Google Scholar 

  101. Prasad K.V.S., Severini A., Kaplan J.G. 1987. Sodium ion fluxes in proliferating lymphocytes: an early component of mitogenic signal. Arch. Biochem. Biophys. 252:515–525

    Article  PubMed  CAS  Google Scholar 

  102. Rajan S., Wischmeter E., Liu G.X., Preisig-Muller R., J. Daut, Karschin A., Derst C. 2000. TASK-3, a novel tandem pore domain acid-sensitive K+ channel. An extracellular histidine as pH sensor. J. Biol. Chem. 275:16650–16657

    Article  PubMed  CAS  Google Scholar 

  103. Rakowski R.F., Sagar S. 2003. Found: Na+ and K+ binding sites of the sodium pump. News Physiol. Sci. 18:164–168

    PubMed  CAS  Google Scholar 

  104. Rishal I., Keren-Raifman T., Yakubovich D., Ivanina T., Dessauer C.W., Slepak V. Z., Dascal N. 2003. Na+ promotes the dissociation between GαGDP and Gβγ, activating G-protein-gated K+ channels. J. Biol. Chem. 278:3840–3845

    Article  PubMed  CAS  Google Scholar 

  105. Robison G.A., Butcher R.W., Sutherland E.W. 1971. Cyclic AMP. Academic Press, New York

    Google Scholar 

  106. Rose C.R., Konnerth A. 2001. NMDA-receptor-mediated Na+ signals in spines and dendrites. J. Neurosci. 21:4207–4214

    PubMed  CAS  Google Scholar 

  107. Runkel L., Shaw P.E., Herrera R.E., Hipskind R.A., Norheim A. 1991. Multiple basal promoter elements determine the level of human c-fos transcription. Mol. Cell. Biol. 11:1270–1280

    PubMed  CAS  Google Scholar 

  108. Russell J.M. 2000. Sodium-potassium-chloride cotransport. Physiol. Rev. 80:212–276

    Google Scholar 

  109. Ryazanov A.G. 2002. Elongation factor-2 kinase and its newly discovered relatives. FEBS Lett. 514:26–29

    Article  PubMed  CAS  Google Scholar 

  110. Ryazanov A.G., Shestakova E.A., Natapov P.G. 1988. Phosphorylation of elongation factor 2 by EF-2 kinase affects rate of translation. Nature 334:170–173

    Article  PubMed  CAS  Google Scholar 

  111. Schmidlin O., Tanaka M., Bollen A.W., Yi S.L., Morris R.B. 2005. Chloride-dominant salt sensitivity in the stroke-prone spontaneously hypertensive rat. Hypertension 45:867–873

    Article  PubMed  CAS  Google Scholar 

  112. Siesjo B.K., Katsura K., Kristian T. 1996. Acidosis-related damage. Adv. Neurol. 71:209–223

    PubMed  CAS  Google Scholar 

  113. Sutherland E.W. 1972. Studies on the mechanism of hormone action. Science 177:401–408

    PubMed  CAS  Google Scholar 

  114. Takano S., Wadhwa R., Yoshii Y., Nose T., Kaul S.C., Mitsui Y. 1997. Elevated level of mortalin expression in human brain tumors. Exp. Cell Res. 237:38–45

    Article  PubMed  CAS  Google Scholar 

  115. Taurin S., Dulin N.O., Pchejetski D., Grygorczyk R., Tremblay J., Hamet P., Orlov S. N. 2002. c-Fos expression in ouabain-treated vascular smooth muscle cells from rat aorta: evidence for an intracellular-sodium-mediated, calcium-independent mechanism. J. Physiol. 543:835–847

    Article  PubMed  CAS  Google Scholar 

  116. Taurin S., Hamet P., Orlov S.N. 2003. Na/K pump and intracellular monovalent cations: novel mechanism of excitation-transcription coupling involved in inhibition of apoptosis. Mol. Biol. 37:371–381

    Article  CAS  Google Scholar 

  117. Taurin S., Seyrantepe V., Orlov S.N., Tremblay T.-L., Thibaut P., Bennett M. R., Hamet, P. et al. 2002. Proteome analysis and functional expression identify mortalin as an anti-apoptotic gene induced by elevation of [Na+]i/[K+]i ratio in cultured vascular smooth muscle cells. Circ. Res. 91:915–922

    Article  PubMed  CAS  Google Scholar 

  118. Treharne K.J., Riemen C.E., Marshall L.J., Muimo R., Mehta A. 2001. Nucleoside diphosphate kinase – a component of the [Na+]- and [Cl−]-sensitive phosphorylation cascade in human and murine airway epithelium. Pfluegers Arch. 443:S97–S102

    Article  CAS  Google Scholar 

  119. Tremblay J., Gerzer R., Vinay P., Pang S.C., Beliveau R., Hamet P. 1985. The increase of cGMP by atrial natriuretic factor correlates with the distribution of particulate guanylate cyclase. FEBS Letters 181:17–22

    Article  PubMed  CAS  Google Scholar 

  120. Trevisi L., Visentin B., Cusinato F., Pighin I., Luciani S. 2004. Antiapoptotic effect of ouabain on human umbilical endothelial cells. Biochem. Biophys. Res. Commun. 321:716–721

    Article  PubMed  CAS  Google Scholar 

  121. Uehara Y., Numabe A., Kawabata Y., Nagata T., Hirawa N., Ishimutsu T., Matsuoka, H. et al. 1991. Rapid smooth muscle cell growth and endogenous prostaglandin system in spontaneously hypertensive rats. Am. J. Hypertens. 4:806–814

    PubMed  CAS  Google Scholar 

  122. Wadhwa R., Pereira-Smith O.M., Reddel R.R., Sugimoto Y., Mitsui Y., Kaul S.C. 1995. Correlation between complementation group for immortality and the cellular distribution of mortalin. Exp. Cell Res. 216:101–106

    Article  PubMed  CAS  Google Scholar 

  123. Wadhwa R., Takano S., Mitsui Y., Kaul S. C. 1999. NIH 3T3 cells malignantly transformed by mot-2 show inactivation and cytoplasmic sequestration of the p53 proteins. Cell Res. 9:261–269

    Article  PubMed  CAS  Google Scholar 

  124. Wadhwa R., Takano S., Robert M., Yoshida A., Nomura H., Reddel R.R., Mitsui, Y. et al. 1998. Inactivation of tumor suppressor p53 by Mot-2, a hsp70 family member. J. Biol. Chem. 273:29586–29591

    Article  PubMed  CAS  Google Scholar 

  125. Wakabayashi S., Shigekawa M., Poyssegur J. 1997. Molecular physiology of vertebrate Na+/H+ exchanger. Physiol. Rev. 77:51–74

    PubMed  CAS  Google Scholar 

  126. Williams R.S., Benjamin I.J. 2000. Protective responses in the ischemic myocardium. J. Clin. Invest. 106:813–818

    Article  PubMed  CAS  Google Scholar 

  127. Wilson F.H., Disse-Nicodeme S., Choate K.A., Ishikawa K., Nelson-Williams C., Desitter I., Gunel, M. et al. 2001. Human hypertension caused by mutations in WNK kinases. Science 293:1107–1112

    Article  PubMed  CAS  Google Scholar 

  128. Xie Z., Askari A. 2002. Na+/K+-ATPase as a signal transducer. Eur. J. Biochem. 269:2434–2439

    Article  PubMed  CAS  Google Scholar 

  129. Xiong Z.-G., Zhu X.-M., Chu X.-P., Minami M., Hey J., Wei W.-L., MacDonald, J.F. et al. 2004. Neuroprotection in ishemia: blocking calcium-permeable acid-sensitive ion channels. Cell 118:687–698

    Article  PubMed  CAS  Google Scholar 

  130. Yu X.-M., Salter M. B. 1998. Gain control of NMDA-receptor currents by intracellular sodium. Nature 396:469–474

    Article  PubMed  CAS  Google Scholar 

  131. Zhou X., Jiang G., Zhao A., Bondeva T., Hirzel P., Balla T. 2001. Inhibition of Na,K-ATPase activates PI3 kinase and inhibits apoptosis in LLC-PK1 cells. Biochem. Biophys. Res. Commun. 285:46–51

    Article  PubMed  CAS  Google Scholar 

  132. Zippin J. H., Farrell J., Huron D., Kamenetsy M., Hess K.C., Fischman D.A., Levin, L.R. et al. 2004. Bicarbonate-responsive “soluble” adenylyl cyclase defines a nuclear cAMP microdomain. J. Cell Biol. 164:527–534

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada and the Kidney Foundation of Canada. The editorial help of Ovid Da Silva’ Research Support Office, CHUM, is appreciated.

Author information

Authors and Affiliations

  1. Centre de recherche, Centre hospitalier de l’Université de Montréal, (CHUM)-Hôtel-Dieu, Montreal, Quebec, Canada

    S.N. Orlov & P. Hamet

  2. Laboratory of Pathophysiology of Ion Transport Disorders, Centre de recherche , CHUM - Hôtel-Dieu, 3850 rue St-Urbain, Montreal, Quebec, H2W 1T7, Canada

    S.N. Orlov

Authors
  1. S.N. Orlov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. Hamet
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S.N. Orlov.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Orlov, S., Hamet, P. Intracellular Monovalent Ions as Second Messengers. J Membrane Biol 210, 161–172 (2006). https://doi.org/10.1007/s00232-006-0857-9

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00232-006-0857-9

Keywords

Search

Navigation