Skip to main content

Calcium Chelators and Calcium Ionophores

  • Chapter

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 83))

Abstract

The preceding chapters in this volume have demonstrated that Ca ions play critical roles in the regulation of a very large number of physiologic, pharmacologic, and biochemical processes. In the study of these processes, it is invariably necessary to control and measure or monitor the free [Ca2+] with a high degree of precision. Many of these processes are sensitive to submicromolar levels of Ca2+, where endogenous or contaminant Ca2+ can become a significant problem. Therefore, in these instances it becomes especially important to control the concentration of free calcium with buffers. Thus, calcium chelators have played a crucial role in allowing progress in the understanding of Ca2+-regulated processes. Chelators are extensively utilized to buffer free [Ca2+] just as pH buffers are utilized to buffer low concentrations of protons. Calcium chelators which exhibit changes in their optical properties can be used as buffers and indicators of free [Ca2+] and those which are hydrophobic in nature can be used as Ca ionophores to alter (or control) free [Ca2+] inside cells, organelles, or vesicles. Additionally, these ionophores can be incorporated into synthetic membranes and can be used in Ca2+-selective electrodes (and microelectrodes) to measure free [Ca2+]. The present chapter will discuss some salient properties of these Ca2+ chelators which are important in their experimental use.

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

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight 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

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Albert A (1953) Avidity of terramycin and aureomycin for metallic cations. Nature 172:201

    Article  PubMed  CAS  Google Scholar 

  • Al-Jabore A, Roufogalis BD (1981) Influence of EGTA on the apparent Ca2+ affinity of Mg2+-dependent, Ca2+-stimulated ATPase in the human erythrocyte membrane. Biochim Biophys Acta 645:1–9

    Article  Google Scholar 

  • Allen DG, Blinks JR (1979) The interpretation of light signals from aequorin-injected skeletal and cardiac muscle a new method of calibration. In: Ashley CC, Campbell AK (eds) Detection and measurements of free Ca2+ in cells. Elsevier/North Holland, Amsterdam, pp 159–174

    Google Scholar 

  • Beeler TJ, Schibeci A, Martonosi A (1980) The binding of arsenazo III to cell components. Biochim Biophys Acta 629:317–327

    Article  PubMed  CAS  Google Scholar 

  • Berger J, Rachlin AI, Scott WE, Sternbach LH, Goldberg MW (1951) The isolation of three new crystalline antibiotics from streptomyces. J Am Chem Soc 73:5295–5298

    Article  Google Scholar 

  • Berman MC (1982 a) Stimulation of calcium transport of sarcoplasmic reticulum vesicles by the calcium complex of ethylene glycol bis(β-aminoethylether)N,N,N′,N′-tetraacetic acid. J Biol Chem 257:1953–1957

    PubMed  CAS  Google Scholar 

  • Berman MC (1982 b) Energy coupling and uncoupling of active calcium transport by sarcoplasmic reticulum membrane. Biochim Biophys Acta 694:95–121

    PubMed  CAS  Google Scholar 

  • Bers DM (1982) A simple method for the accurate determination of free [Ca] in Ca-EGTA solutions. Am J Physiol 242:C404–C408

    PubMed  CAS  Google Scholar 

  • Blinks JR, Weir WG, Hess P, Prendergast FG (1982) Measurement of Ca2+ concentrations in living cells. Prog Biophys Mol Biol 40:1–114

    Article  PubMed  CAS  Google Scholar 

  • Boyd S, Bryson A, Nancollas GH, Torrance K (1965) Thermodynamics of ion association. XII. EGTA complexes with divalent metal ions. J Chem Soc London 5:7353–7358

    Google Scholar 

  • Case GD, Vanderkooi JM, Scarpa A (1974) Physical properties of biological membranes determined by the fluorescence of the calcium ionophore A23187. Arch Biochem Biophys 162:174–185

    Article  PubMed  CAS  Google Scholar 

  • Caswell AH, Pressman BC (1972) Kinetics of transport of divalent cations across sarcoplasmic reticulum vesicles induced by ionophores. Biochem Biophys Res Commun 49:292–298

    Article  PubMed  CAS  Google Scholar 

  • Chiu VCK, Haynes D (1980) The pH dependence and binding equilibria of the calcium indicator-arsenazo III. Membr Biochem 3:169–183

    Article  PubMed  CAS  Google Scholar 

  • Cornelius A, Gartner W, Haynes DH (1974) Cation complexation by valinomycin- and nigericin-type ionophores registered by the fluorescence signal of Tl+. Biochemistry 13:3052–3057

    Article  PubMed  CAS  Google Scholar 

  • Debono M, Molloy RM, Dorman DE, Paschal JW, Babcock DF, Deber CM, Pfeiffer DR (1981) Synthesis and characterization of halogenated derivatives of the ionophore A23187: enhanced calcium ion transport specificity by the 4-bromo derivative. Biochemistry 20:6865–6872

    Article  PubMed  CAS  Google Scholar 

  • Degani H, Friedman HL, Navon G, Kosower EM (1973) Fluorimetric complexing constants and circular dichroism measurements for antibiotic X-537A with univalent and bivalent cations. J Chem Soc Chem Comm 1973:431–432

    Article  Google Scholar 

  • Devore DI, Nastuk WL (1975) Effects of “calcium ionophore” X537A on frog skeletal muscle. Nature 253:644–646

    Article  PubMed  CAS  Google Scholar 

  • Dobler M (1981) Ionophores and their structure. Wiley Interscience, New York

    Google Scholar 

  • Dorogi PL, Moss K, Neumann E (1981) Spectrophotometric determination of reaction stoichiometry and equilibrium constants of metallochromic indicators. Biophys Chem 14:91–100

    Article  PubMed  CAS  Google Scholar 

  • Fabiato A (1985) Time and calcium dependence of activation and inactivation of calcium-induced release of calcium from the sarcoplasmic reticulum of a skinned canine cardiac Purkinje cell. J Gen Physiol 85:247–289

    Article  PubMed  CAS  Google Scholar 

  • Flatman PW, Lew VL (1977) Does ionophore A23187 mediate Na transport in the absence of divalent cations? Nature 270:444–445

    Article  PubMed  CAS  Google Scholar 

  • Grynkiewicz G, Poenie M, Tsien RY (1985) A new generation of Ca2+ indicators with greatly improved fluorescent properties. J Biol Chem 260:3440–3450

    PubMed  CAS  Google Scholar 

  • Harafuji H, Ogawa Y (1980) Re-examination of the apparent binding constant of ethylene glycol bis(β-aminoethyl ethylene)-N,N,N′,N′-tetraacetic acid with calcium around neutral pH. J Biochem 87:1305–1312

    PubMed  CAS  Google Scholar 

  • Harned HS, Owen BB (1958) The physical chemistry of electrolytic solutions, 2nd edn. Reinhold, New York, p 575

    Google Scholar 

  • Harrison SM, Bers DM (1987) The effect of temperature and ionic strength on the apparent Ca-affinity of EGTA and the analogous Ca-Chelators BAPTA and dibromo-BAPTA. Biochim Biohpys Acta 925:133–143

    Article  CAS  Google Scholar 

  • Hellam DC, Podolsky RJ (1969) Force measurements in skinned muscle fibres. J Physiol (Lond) 200:807–819

    CAS  Google Scholar 

  • Hinds TR, Vincenzi FF (1985) The effect of ETH 1001 on ion fluxes across red blood cell membranes. Cell Calcium 6:265–279

    Article  PubMed  CAS  Google Scholar 

  • Illingworth JA (1981) A common source of error in pH measurements. Biochem J 195:259–262

    PubMed  CAS  Google Scholar 

  • Kotagel N, Colca JR, McDaniel ML (1983) Activation of an islet cell plasma membrane (Ca2+ + Mg2+)-ATPase by calmodulin and Ca-EGTA. J Biol Chem 258:4808–4813

    Google Scholar 

  • Liu C, Hermann TE (1978) Characterization of ionomycin as a calcium ionophore. J Biol Chem 253:5892–5894

    PubMed  CAS  Google Scholar 

  • Liu WC, Shesarchyk DS, Ashe G, Trejo WH, Brown WE, Meyers E (1978) Ionomycin, a new polyether antibiotic. J Antibiot (Tokyo) 31:815–819

    CAS  Google Scholar 

  • Martell AE, Smith RM (1974) Critical stability constants, vol 1. Plenum, New York

    Google Scholar 

  • Martell AE, Smith RM (1977) Critical stability constants, vol 3. Plenum, New York

    Google Scholar 

  • Mathew MK, Balaram P (1980) A reinvestigation of Chlortetracycline fluorescence: effect of pH, metal ions and environment. J Inorgan Biochem 13:339–346

    Article  CAS  Google Scholar 

  • Meier PC, Lanter F, Ammann D, Steiner RA, Simon W (1982) Applicability of available ion-selective liquid-membrane microelectrodes to intracellular ion-activity measurements. Pflügers Arch 393:23–30

    Article  PubMed  CAS  Google Scholar 

  • Miller DJ, Smith GL (1984) EGTA purity and the buffering of calcium ions in physiological solutions. Am J Physiol 246:C160–C166

    PubMed  CAS  Google Scholar 

  • Morf WE, Simon W (1971) Berechnung von freien Hydratationsenthalpien und Koordinationszahlen für Kationen aus leicht zugänglichen Parametern. Helv Chem Acta 54:794–810

    Article  CAS  Google Scholar 

  • Nakon R (1979) Free metal ion depletion by Good’s buffers. Anal Biochem 95:527–532

    Article  PubMed  CAS  Google Scholar 

  • Oehme M, Kessler M, Simon W (1976) Neutral carrier Ca2+-microelectrode. Chimia 30:204–206

    CAS  Google Scholar 

  • Ogawa Y, Harafjuji H, Kurebayashi N (1980) Comparison of the characteristics of four metallochromic dyes as potential calcium indicators for biological experiments. J Biochem 87:1293–1303

    PubMed  CAS  Google Scholar 

  • Ohnishi ST (1978) Characterization of the murexide method: dual wavelength spectrophotometry of cations under physiological conditions. Anal Biochem 85:165–179

    Article  PubMed  CAS  Google Scholar 

  • Ohnishi ST (1979 a) Interaction of metallochromic indicators with calcium sequestering organelles. Biochim Biophys Acta 585:315–319

    Article  PubMed  CAS  Google Scholar 

  • Ohnishi ST (1979 b) A method of estimating the amount of calcium bound to the metallochromic indicator arsenazo III. Biochim Biophys Acta 586:217–230

    Article  PubMed  CAS  Google Scholar 

  • Palade P, Vergara J (1983) Stoichiometrics of arsenazo III-Ca complexes. Biophys J 43:355–369

    Article  PubMed  CAS  Google Scholar 

  • Pfeiffer DR, Lardy HA (1976) Ionophore A23187: the effect of H+ concentration on complex formation with divalent and monovalent cations and the demonstration of K+ transport in mitochondria mediated by A23187. Biochemistry 15:935–943

    Article  PubMed  CAS  Google Scholar 

  • Pfeiffer DR, Reed PW, Lardy HA (1979) Ultraviolet and fluorescent spectral properties of the divalent cation ionophore A23187 and its metal ion complexes. Biochemistry 13:4007–4014

    Article  Google Scholar 

  • Pressman BC (1973) Properties of ionophores with broad range cation selectivity. Fed Proc 32:1698–1703

    PubMed  CAS  Google Scholar 

  • Pressman BC (1976) Biological applications of ionophores. Ann Rev Biochem 45:501–530

    Article  PubMed  CAS  Google Scholar 

  • Puskin JS, Gunter TE (1975) Electron paramagnetic resonance of copper ion and manganese ion complexes with the ionophore A23187. Biochemistry 14:187–191

    Article  PubMed  CAS  Google Scholar 

  • Reed PW, Lardy HA (1972) A23187: a divalent cation ionophore. J Biol Chem 247:6970–6977

    PubMed  CAS  Google Scholar 

  • Rios E, Schneider MF (1981) Stoichiometry of the reactions of calcium with the metal-lochromic indicator dyes antipyralazo III and arsenazo III. Biophys J 36:607–621

    Article  PubMed  CAS  Google Scholar 

  • Ruzicka J, Hanse EH, Tjell JC (1973) Selectrode — the universal ion-selective electrode. Part IV: The calcium (II) selectrode employing a new ion exchanger in a non-porous membrane and a solid state reference system. Anal Chim Acta 67:155–178

    Article  CAS  Google Scholar 

  • Sarkadi B, Shubert A, Gardos G (1979) Effects of Ca-EGTA buffers on active calcium transport in inside-out red cell membrane vesicles. Experientia 35:1045–1047

    Article  PubMed  CAS  Google Scholar 

  • Scarpa A (1979) Measurement of calcium ion concentrations with metallochromic indicators. In: Ashley CC, Campbell AK (eds) Detection and measurement of free Ca2+ in cells. Elsevier/North Holland, Amsterdam, pp 85–115

    Google Scholar 

  • Scarpa A, Brinley FJ, Dubyak G (1978) Antipyralazo III, a middle range Ca2+ metallochromic indicator. Biochemistry 17:1378–1386

    Article  PubMed  CAS  Google Scholar 

  • Schefer U, Ammann D, Pretsch E, Oesch U, Simon W (1986) Neutral carrier based Ca2+-selective electrode with detection limit in the sub-nanomolar range. Anal Chem 58:2282–2285

    Article  CAS  Google Scholar 

  • Schwarzenbach VG, Seen H, Anderegg G (1957) Komplexone XXIX. Ein grosser Chelateffekt besonderer Art. Helv Chim Acta 40:1886–1900

    Article  CAS  Google Scholar 

  • Shimomura O, Shimomura A (1984) Effect of calcium chelators on the Ca2+-dependent luminescence of aequorin. Biochem J 221:907–910

    PubMed  CAS  Google Scholar 

  • Simon W, Morf WE, Ammann D (1977) Calcium ionophores. In: Wasserman RH, Corradino RA, Carafoli E, Kretsinger RH, MacLennan DH, Siegel FL (eds) Calcium binding proteins and calcium function. Elsevier North-Holland, Amsterdam, pp 50–62

    Google Scholar 

  • Simon W, Ammann D, Oehme M, Morf WE (1978) Calcium-selective electrodes. Ann NY Acad Sci 307:52–69

    Article  CAS  Google Scholar 

  • Smith PD, Berger RL, Podolsky RJ (1977) Stopped-flow study of the rate of calcium binding by EGTA. Biophys J 17:159a

    Google Scholar 

  • Toeplitz BA, Cohen AI, Funke PT, Parker WL, Gougaitas JZ (1979) Structure of ionomycin — a novel diacidic polyether antibiotic having high affinity for calcium ions. J Am Chem Soc 101:3344–3353

    Article  CAS  Google Scholar 

  • Trosper TL, Philipson KD (1984) Stimulatory effect of calcium chelators on Na+-Ca2+ exchange in cardiac sarcolemmal vesicles. Cell Calcium 5:211–222

    Article  PubMed  CAS  Google Scholar 

  • Truter MR (1976) Chemistry of calcium ionophores. Symp Soc Exp Biol 30:19–40

    CAS  Google Scholar 

  • Tsien RY (1980) New calcium indicators and buffers with high selectivity against magnesium and protons: design, synthesis and properties of prototype structures. Biochemistry 19:2396–2404

    Article  PubMed  CAS  Google Scholar 

  • Tsien RY (1983) Intracellular measurements of ion activities. Annu Rev Biophys Bioeng 12:91–116

    Article  PubMed  CAS  Google Scholar 

  • Tsien RY, Rink TJ (1980) Neutral carrier ion-selective microelectrodes for measurement of intracellular free calcium. Biochim Biophys Acta 599:623–638

    Article  PubMed  CAS  Google Scholar 

  • Tsien RY, Pozzan T, Rink TJ (1982 a) T-cell mitogens cause early changes in cytoplasmic free Ca2+ and membrane potential in lymphocytes. Nature 295:68–71

    Article  PubMed  CAS  Google Scholar 

  • Tsien RY, Pozzan T, Rink TJ (1982 b) Calcium homeostasis in intact lymphocytes: cytoplasmic free calcium monitored with a new intracellularly trapped fluorescent indicator. J Cell Biol 94:325–334

    Article  PubMed  CAS  Google Scholar 

  • Waisman DM, Gimble JM, Goodman DBP, Rasmussen H (1981) Studies of the Ca2+ transport mechanism of human erythrocyte inside-out plasma membrane vesicles. J Biol Chem 256:409–414

    PubMed  CAS  Google Scholar 

  • White JR, Pierce FL (1982) Characterization of Chlortetracycline (aureomycin) as a calcium ionophore. Biochemistry 21:6309–6312

    Article  PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1988 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Bers, D.M., MacLeod, K.T. (1988). Calcium Chelators and Calcium Ionophores. In: Baker, P.F. (eds) Calcium in Drug Actions. Handbook of Experimental Pharmacology, vol 83. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-71806-9_23

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-71806-9_23

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-71808-3

  • Online ISBN: 978-3-642-71806-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics