Skip to main content
SpringerLink
Log in

Cellular Mg2+ Transport and Homeostasis: An Overview

  • Chapter
New Perspectives in Magnesium Research

Abstract

Magnesium plays a vital role as a cofactor for many enzymes, as a binding partner of nucleotides, and in stabilizing nucleic acids and membranes. It acts as a modulator of ion channels, and it affects many other cellular processes such as neuromuscular excitability, secretion of hormones, and it antagonizes the actions of Ca2+, to name a few effects.1–4 Mg2+ deficiency was found to be associated with hypertension, ischemic heart disease, infl ammation, eclampsia, diabetes, cystic fibrosis, and in the establishment of human immunodeficiency virus 1 (HI V-1) reservoirs.5–10 Several disease phenotypes have been shown to be due to inherited disorders of Mg2+ homeostasis.11–15 Therefore, the regulation of extracellular and intracellular magnesium levels by transmembrane and transepithelial transport processes is critical for numerous cellular and organ functions.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 269.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Hartwig A. Role of magnesium in genomic stability. Mutation Res 2001;475:113–121.

    PubMed  CAS  Google Scholar 

  2. Bara M, Guiet-Bara A. Magnesium regulation of Ca2+channels in smooth muscle and endothelial cells of human allantochorial placental vessels. Magnes Res 2001;14:11–18.

    PubMed  CAS  Google Scholar 

  3. White RE, Hartzell HC. Magnesium ions in cardiac function. Regulator of ion channels and second messengers. Biochem Pharmacol 1989;38:859–867.

    Article  PubMed  CAS  Google Scholar 

  4. Mooren FC, Turi S, Günzel D, et al. Calcium-magnesium interactions in pancreatic acinal cells. FASEB J 2001;15:659–672.

    Article  PubMed  CAS  Google Scholar 

  5. Altura BM, Altura BT. Magnesium and cardiovascular biology: an important link between cardiovascular risk factors and atherogenesis. Cell Mol Biol Res 1995;41:347–359.

    PubMed  CAS  Google Scholar 

  6. Kisters K, Krefting ER, Barenbrock M, Spieker C, Rahn KH. Na+ and Mg2+ contents in smooth muscle cells in spontaneously hypertensive rats. Am J Hypertens 1999;12:648–652.

    Article  PubMed  CAS  Google Scholar 

  7. Weglicki WB, Phillips TM. Pathobiology of magnesium deficiency: a cytokine/ neurogenic inflammation hypothesis. Am J Physiol 1992;263:R734–R737.

    PubMed  CAS  Google Scholar 

  8. Saris NE, Mervaala E, Karppanen H, Khawaja JA, Lewenstam A. Magnesium. An update on physiological, clinical and analytical aspects. Clin Chim Acta 2000;294: 1–26.

    Article  PubMed  CAS  Google Scholar 

  9. Vormann J. Mineral metabolism in erythrocytes from patients with cystic fibrosis. Eur J Clin Chem Clin Biochem 1992;30:193–196.

    PubMed  CAS  Google Scholar 

  10. Goldschmidt V, Didierjean J, Ehresmann B, Ehresmann C, Isel C, Marquet R. Mg2+ dependency of HIV-1 reverse transcription, inhibition by nucleoside analogues and resistance. Nucleic Acids Res 2006;34:42–52.

    Article  PubMed  CAS  Google Scholar 

  11. Cole DE, Quamme GA. Inherited disorders of renal magnesium handling. J Am Soc Nephrol 2000;11:1937–1947.

    PubMed  CAS  Google Scholar 

  12. Schlingmann KP, Konrad M, Seyberth HW. Genetics of hereditary disorders of magnesium homeostasis. Pediatr Nephrol 2004;19:13–25.

    Article  PubMed  Google Scholar 

  13. Hoenderop JG, Bindels RJ. Epithelial Ca2+ and Mg2+ channels in health and disease. J Am Soc Nephrol 2005;16:15–26.

    Article  PubMed  CAS  Google Scholar 

  14. Hermosura MC, Nayakanti H, Dorovkov MV, et al. A TRPM7 variant shows altered sensitivity to magnesium that may contribute to the pathogenesis of two Guamanian neurodegenerative disorders. Proc Natl Acad Sci U S A 2005;102: 11510–11515.

    Article  PubMed  CAS  Google Scholar 

  15. Hou J, Paul DL, Goodenough DA. Paracellin-1 and the modulation of ion selectivity of tight junctions. J Cell Sci 2005;118:5109–5118.

    Article  PubMed  CAS  Google Scholar 

  16. Dai LJ, Raymond L, Friedman PA, Quamme GA. Mechanisms of amiloride stimulation of Mg2+ uptake in immortalized mouse distal convoluted tubule cells. Am J Physiol 1997;272:F249–F256.

    PubMed  CAS  Google Scholar 

  17. Schweigel M, Lang I, Martens H. Mg2+ transport in sheep rumen epithelium: evidence for an electrodiffusive mechanism. Am J Physiol 1999;277:G976–G982.

    PubMed  CAS  Google Scholar 

  18. Quamme GA, Rabkin SW. Cytosolic free magnesium in cardiac myocytes: identification of a Mg2+ influx pathway. Biochem Biophys Res Commun 1990;167:1406–1412.

    Article  PubMed  CAS  Google Scholar 

  19. Okorodudu A, Yang H, Elghetany MT. Ionized magnesium in the homeostasis of cells: intracellular threshold for Mg2+ in human platelets. Clin Chim Acta 2001;303:147–154.

    Article  PubMed  CAS  Google Scholar 

  20. Günther T, Vormann J, Averdunk R. Characterization of furosemide-sensitive Mg2+ influx in Yoshida ascites tumor cells. FEBS Lett 1986;197:297–300.

    Article  PubMed  Google Scholar 

  21. Jüttner R, Ebel H. Characterization of Mg2+ transport in brush border membrane vesicles of rabbit ileum studied with mag-fura-2. Biochem Biophys Acta 1999;1370:51–63.

    Google Scholar 

  22. Schweigel M, Martens H. Anion-dependent Mg2+ influx and a role for a vacuolar H+-ATPase in sheep ruminal epithelial cells. Am J Physiol Gastrointest Liver Physiol 2003;285:G45–G53.

    PubMed  CAS  Google Scholar 

  23. Smith RL, Maguire ME. Microbial magnesium transport: unusual transporters searching for identity. Mol Microbiol 1998;28:217–226.

    Article  PubMed  CAS  Google Scholar 

  24. Nadler MJ, Hermosura MC, Inabe K, et al. LTRPC7 is a Mg.ATP-regulated divalent cation channel required for cell viability. Nature 2001;411:590–595.

    Article  PubMed  CAS  Google Scholar 

  25. Schlingmann KP, Weber S, Peters M, et al. Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family. Nat Genet 2002;31:166–170.

    Article  PubMed  CAS  Google Scholar 

  26. Walder RY, Landau D, Meyer P, et al. Mutation of TRPM6 causes familial hypomagnesemia with secondary hypocalcemia. Nat Genet 2002;31:171–174.

    Article  PubMed  CAS  Google Scholar 

  27. Schmitz C, Perraud AL, Johnson CO, et al. Regulation of vertebrate cellular Mg2+ homeostasis by TRPM7. Cell 2003;114:191–200.

    Article  PubMed  CAS  Google Scholar 

  28. Voets T, Nilius B, Hoefs S, et al. TRPM6 forms the Mg2+ influx channel involved in intestinal and renal Mg2+ absorption. J Biol Chem 2004;279:19–25.

    Article  PubMed  CAS  Google Scholar 

  29. Goytain A, Quamme GA. Identification and characterization of a novel mammalian Mg2+ transporter with channel-like properties. BMC Genomics 2005;6L48.

    Google Scholar 

  30. Goytain A, Quamme GA. Functional characterization of ACDP2 (ancient conserved domain protein), a divalent metal transporter. Physiol Genomics 2005;22:382–389.

    Article  PubMed  CAS  Google Scholar 

  31. Goytain A, Quamme GA. Functional characterization of the human solute carrier, SLC41A2. Biochem Biophys Res Commun 2005;330:701–705.

    Article  PubMed  CAS  Google Scholar 

  32. Goytain A, Quamme GA. Functional characterization of human SLC41A1, a Mg2+ transporter with similarity to prokaryotic MgtE Mg2+ transporters. Physiol Genomics 2005;21:337–342.

    Article  PubMed  CAS  Google Scholar 

  33. Monteilh-Zoller MK, Hermosura MC, Nadler MJ, Scharenberg AM, Penner R, Fleig A. TRPM7 provides an ion channel mechanism for cellular entry of trace metal ions. J Gen Physiol. 2003;121:49–60.

    Article  PubMed  CAS  Google Scholar 

  34. Montell C. Mg2+ homeostasis: the Mg2+nificent TRPM chanzymes. Curr Biol 2003;13:R799–R801.

    Article  PubMed  CAS  Google Scholar 

  35. Schmitz C, Perraud AL, Fleig A, Scharenberg AM. Dual-function ion channel/ protein kinases: novel components of vertebrate magnesium regulatory mechanisms. Pediatr Res 2004;55:734–737.

    Article  PubMed  CAS  Google Scholar 

  36. Chubanov V, Waldegger S, Mederos y Schnitzler M, et al. Disruption of TRPM6/ TRPM7 complex formation by a mutation in the TRPM6 gene causes hypomagnesemia with secondary hypocalcemia. Proc Natl Acad Sci U S A 2004;101:2894–2899.

    Article  PubMed  CAS  Google Scholar 

  37. Schmitz C, Dorovkov MV, Zhao X, Davenport BJ, Ryazanov AG, Perraud AL. The channel kinases TRPM6 and TRPM7 are functionally nonredundant. J Biol Chem 2005;280:37763–37771.

    Article  PubMed  CAS  Google Scholar 

  38. Wang CY, Yang P, Shi JD, et al. Molecular cloning and characterization of the mouse Acdp gene family. BMC Genomics 2004;5:7.

    Article  PubMed  Google Scholar 

  39. Gibson MM, Bagga DA, Miller CG, Maguire ME. Magnesium transport in Salmonella typhimurium: the influence of new mutations conferring Co2+ resistance on the CorA Mg2+ transport system. Mol Microbiol 1991;5:2753–2762.

    Article  PubMed  CAS  Google Scholar 

  40. Yang M, Jensen LT, Gardner AJ, Culotta VC. Manganese toxicity and Saccharomyces cerevisiae Mam3p, a member of the ACDP (ancient conserved domain protein) family. Biochem J 2005;386:479–487.

    Article  PubMed  CAS  Google Scholar 

  41. Wabakken T, Rian E, Kveine M, Aasheim HC. The human solute carrier SLC41A1 belongs to a novel eukaryotic subfamily with homology to prokaryotic MgtE Mg2+ transporters. Biochem Biophys Res Commun 2003;306:718–724.

    Article  PubMed  CAS  Google Scholar 

  42. Smith RL, Thompson LJ, Maguire ME. Cloning and characterization of MgtE, a putative new class of Mg2+ transporter from Bacillus firmus OF4. J Bacteriol 1995;177:1233–1238.

    PubMed  CAS  Google Scholar 

  43. Quamme GA. Control of magnesium transport in the thick ascending limb. Am J Physiol Renal Fluid Electrolyte Physiol 1989;25:F197–F210.

    Google Scholar 

  44. Leonhard-Marek S, Stumpff F, Brinkmann I, Breves G, Martens H. Basolateral Mg2+/Na+ exchange regulates apical nonselective cation channel in sheep rumen epithelium via cytosolic Mg2+. Am J Physiol Gastrontest Liver Physiol 2005;288: G630–G645.

    Article  CAS  Google Scholar 

  45. Tashiro M, Konishi M, Iwamoto T, Shigekawa M, Kurihara S. Transport of magnesium by two isoforms of the Na+-Ca2+ exchanger expressed in CCL39 fibroblasts. Plügers Arch 2000;440:819–827.

    Article  CAS  Google Scholar 

  46. Cefaratti C, Romani A, Scarpa A. Characterization of two Mg2+ transporters in sealed plasma membrane vesicles from rat liver. Am J Physiol 1998;275:C2995–C1008.

    Google Scholar 

  47. Ödblom M P, Handy RD. A novel D I DS-sensitive, anion-dependent Mg2+ efflux pathway in rat ventricular myocytes. Biochem Biophys Res Commun 1999;264: 334–337.

    Article  PubMed  Google Scholar 

  48. Günther T, Vormann J, Förster R. Regulation of intracellular magnesium by Mg2+ efflux. Biochem Biophys Res Commun 1984;119:124–131.

    Article  Google Scholar 

  49. Büttner S, Günther T, Schäfer A, Vormann J. Magnesium metabolism in erythrocytes of various species. Magnes Bull 1998;101–109.

    Google Scholar 

  50. Feray JC, Garay R An Na+-stimulated Mg2+ transport system in human red blood cells. Biochim Biophys Acta 1986;856:76–84.

    Article  PubMed  CAS  Google Scholar 

  51. Flatman P, Smith LM. Magnesium transport in magnesium-loaded ferret red blood cells. Pflügers Arch 1996;432:995–1002.

    Google Scholar 

  52. Fagan T, Romani A. α1-adrenoreceptor-induced Mg2+ extrusion from rat hepatocytes occurs via Na-dependent transport mechanism. Am J Physiol Gastrointest Liver Physiol 2001;280:G1145–G1156.

    PubMed  CAS  Google Scholar 

  53. Günther T, Vormann J. Activation of Na+/Mg2+ antiport in thymocytes by cAMP. FEBS Lett 1992;297:132–134.

    Article  PubMed  Google Scholar 

  54. Hintz K, Günzel D, Schlue W-R. Na+-dependent regulation of the free Mg2+ concentration in neuropile glial cells and P neurones of the leech Hirudo medicinalis. Pflügers Arch 1999;437:354–362.

    Article  PubMed  CAS  Google Scholar 

  55. Zhang GH, Melvin JE. Regulation by extracellular Na+ of cytosolic Mg2+ concentration in Mg2+-loaded rat sublingual acini. FEBS Lett 1995;371:52–56.

    Article  PubMed  CAS  Google Scholar 

  56. Schweigel M, Park HS, Etschmann B, Martens H. Characterization of the Na+-dependent Mg2+ transport in sheep ruminal epithelial cells. Am J Physiol Gastrointest Liver Physiol 2006;290:G56–G65.

    Article  PubMed  CAS  Google Scholar 

  57. Yoshimura M, Oshima T, Matsuura H, et al. Effect of transmembrane gradient of magnesium and sodium on the regulation of cytosolic free magnesium concentration in human platelets. Clin Sci 1995;89:293–298.

    PubMed  CAS  Google Scholar 

  58. Frenkel EJ, Graziani M, Schatzmann HJ. ATP requirement of the sodiumdependent magnesium extrusion from human red blood cells. J Physiol 1989;414:385–397.

    PubMed  CAS  Google Scholar 

  59. Schweigel M, Vormann J, Martens H. Mechanisms of Mg2+ transport in cultured ruminal epithelial cells. Am J Physiol Gastrointest Liver Physiol 2000;278: G400–G408.

    PubMed  CAS  Google Scholar 

  60. Kubota T, Tokuno K, Nakagawa J, et al. Na /Mg2+ transporter acts as a Mg2+ buffering mechanism in PC12 cells. Biochem Biophys Res Commun 2003;303:332–336.

    Article  PubMed  CAS  Google Scholar 

  61. Cefaratti C, Romani A, Scarpa A. Differential localization and operation of distinct Mg2+ transporters in apical and basolateral sides of rat liver plasma membrane. J Biol Chem 2000;275:3772–3780.

    Article  PubMed  CAS  Google Scholar 

  62. Günther T, Vormann J. Mg2+ efflux is accomplished by an amiloride-sensitive Na /Mg2+ antiport. Biochem Biophys Res Commun 1985;130:540–545.

    Article  PubMed  Google Scholar 

  63. Günther T. Putative mechanism of Mg2+/Mg2+ exchange and Na /Mg2+ antiport. Magnes Bull 1996;18:2–6.

    Google Scholar 

  64. Handy RD, Gow IF, Ellis D, Flatman PW. Na-dependent regulation of intracellular free magnesium concentration in isolated rat ventricular myocytes. J Mol Cell Cardiol 1996;28:1641–1651.

    Article  PubMed  CAS  Google Scholar 

  65. Tashiro M, Konishi M. Na+ gradient-dependent Mg2+ transport in smooth muscle cells of guinea pig tenia cecum. Biophys J 1997;73:3371–3384.

    Article  PubMed  CAS  Google Scholar 

  66. Willis JS, Xu W, Zhao Z. Diversities of transport of sodium in rodent red cells. Comp Biochem Physiol 1992;102:609–614.

    Article  CAS  Google Scholar 

  67. Fatholahi M, LaNoue K, Romani A, Scarpa A. Relationship between total and free cellular Mg2+ during metabolic stimulation of rat heart myocytes and perfused hearts. Arch Biochem Biophys 2000;374:395–401.

    Article  PubMed  CAS  Google Scholar 

  68. Romani A, Scarpa A. Norepinephrine evokes a marked Mg2+ efflux from liver cells. FEBS Lett 1990;269:37–40.

    Article  PubMed  CAS  Google Scholar 

  69. Matsuura T, Kanayama Y, Inoue T, Takeda T, Morishima I. cAMP-induced changes of intracellular free Mg2+ levels in human erythrocytes. Biochim Biophys Acta 1993;1220:31–36.

    Article  PubMed  CAS  Google Scholar 

  70. Wolf FI, Di Francesco A, Covacci V, Cittadani, A. Regulation of Na-dependent magnesium efflux from intact tumor cells. Magnes Res 1995;(Suppl 1):490–496.

    Google Scholar 

  71. Romani A, Dowell E, Scarpa A. Cyclic AMP induced Mg2+ release from rat liver hepatocytes, permeabilized hepatocytes and isolated mitochondria. J Biol Chem 1991;266:24376–24384.

    PubMed  CAS  Google Scholar 

  72. He Y, Yao G, Savoia C, Touyz RM. Transient receptor potential melastatin 7 ion channels regulate magnesium homeostasis in vascular smooth muscle cells. Role of angiotensin II. Circ Res 2005;96:207–215.

    Article  PubMed  CAS  Google Scholar 

  73. Schweigel M, Buschmann F, Etschmann B, Vormann J. Development of monoclonal antibodies directed against the Na /Mg2+-antiporter and their use in ruminal epithelial cells. Proc Soc Nutr Physiol 2005;13:94.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Veterinary-Physiology, Free University of Berlin, Berlin, Germany

    Martin Kolisek PhD

  2. Max F. Perutz Laboratories, University of Vienna, Vienna, Austria

    Rudolf J. Schweyen PhD

  3. Department of Nutritional Physiology “Oskar Kellner”, Research Institute for the Biology of Farm Animals — FBN, Dummerstorf, Germany

    Monika Schweigel PhD

Authors
  1. Martin Kolisek PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rudolf J. Schweyen PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Monika Schweigel PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan

    Yoshiki Nishizawa MD, PhD (Dean of Medicine, Professor of Internal Medicine) (Dean of Medicine, Professor of Internal Medicine)

  2. Osaka City University, Osaka, Japan

    Hirotoshi Morii MD, PhD (Emeritus Professor) (Emeritus Professor)

  3. Université Pierre et Marie Curie, Paris, France

    Jean Durlach MD, PhD (President of the International Society for the Development of Research on Magnesium (SDRM), Editor-in-Chief Magnesium Research journal) (President of the International Society for the Development of Research on Magnesium (SDRM), Editor-in-Chief Magnesium Research journal)

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer-Verlag London Limited

About this chapter

Cite this chapter

Kolisek, M., Schweyen, R.J., Schweigel, M. (2007). Cellular Mg2+ Transport and Homeostasis: An Overview. In: Nishizawa, Y., Morii, H., Durlach, J. (eds) New Perspectives in Magnesium Research. Springer, London. https://doi.org/10.1007/978-1-84628-483-0_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-84628-483-0_3

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-84628-388-8

  • Online ISBN: 978-1-84628-483-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation