Download PDF
Thromb Haemost 1978; 40(02): 212-218
DOI: 10.1055/s-0038-1648654
VIth International Congress on Thrombosis and Haemostasis
Schattauer GmbH Stuttgart

Movement of Calcium Ions and their Role in the Activation of Platelets[*]

P Massini
The Theodor Kocher Institute, University of Berne, Berne, Switzerland
,
R Käser-Glanzmann
The Theodor Kocher Institute, University of Berne, Berne, Switzerland
,
E F Lüscher
The Theodor Kocher Institute, University of Berne, Berne, Switzerland
› Author Affiliations
Further Information

Publication History

Publication Date:
12 July 2018 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

The increase of the cytoplasmic Ca-concentration plays a central role in the initiation of platelet activation. Four kinds of movements of Ca-ions are presumed to occur during this process: a) Ca-ions liberated from membranes induce the rapid shape change, b) Vesicular organelles release Ca-ions into the cytoplasm which initiate the release reaction, c) The storage organelles called dense bodies, secrete their contents including Ca-ions to the outside during the release reaction, d) At the same time a rearrangement of the plasma membrane occurs, resulting in an increase in its permeability for Ca-ions as well as in an increase in the number of Ca-binding sites.

Since most processes occurring during platelet activation are reversible, the platelet must be equipped with a mechanism which removes Ca-ions from the cytoplasm. A vesicular fraction obtained from homogenized platelets indeed accumulates Ca actively. This Ca- pump is stimulated by cyclic AMP and protein kinase; it may be involved in the recovery of platelets after activation.

It becomes increasingly clear that the various manifestations of platelet activation are triggered by a rise in the cytoplasmic Ca2+-concentration. The evidence for this and possible mechanisms involved are discussed in some detail in the contributions by Detwiler et al. and by Gerrard and White to this symposium. In this article we shall discuss four different types of mobilization of Ca-ions which occur in the course of the activation of platelets. In addition, at least one transport step involved in the removal of Ca2+ must occur during relaxation of activated platelets.

* Invited Symposium V “Platelets: Intravascular Control Mechanisms” presented to VIth International Congress on Thrombosis and Haemostasis, philadelphia, U. S. A. June 1977


 

  • References

  • 1 Borisy GG, Olmstead JB, Marcum JM, Allen C. 1974; Microtubule assembly in vitro. Federation Proceedings 33: 167
    PubMedGoogle Scholar
  • Carafoli E, Clementi F, Drabikowski W, Margreth A. 1975. Calcium transport in contraction and secretion. North Holland Publications Co; Amsterdam:
    Google Scholar
  • 3 Charo IF, Feinman RD, Detwiler TC. 1976; Inhibition of platelet secretion by an antagonist of intracellular calcium. Biochemical and Biophysical Research Communications 72: 1462
    CrossrefPubMedGoogle Scholar
  • 4 Cohen I, Cohen C. 1972; A tropomyosin-like protein from human platelets. Journal of Molecular Biology 68: 383
    CrossrefPubMedGoogle Scholar
  • 5 Detwiler TC, Feinman RD. 1973; Kinetics of the thrombin-induced release of adenosine triphosphate by platelets. Comparison with release of calcium. Biochemistry 12: 2462
    PubMedGoogle Scholar
  • 6 Douglas WW. 1968; Stimulus-secretion coupling: the concept and clues from chromaffin and other cells. British Journal of Pharmacology 34: 451
    CrossrefPubMedGoogle Scholar
  • 7 Ebashi S, Endo M, Ohtsuki I. 1969; Control of muscle contraction. Quarterly Review of Biophysics 2: 351
    CrossrefPubMedGoogle Scholar
  • 8 Feinman RD, Detwiler TC. 1974; Platelet secretion induced by divalent cation ionophores. Nature 249: 172
    CrossrefPubMedGoogle Scholar
  • 9 Grette K. 1962; Studies on the mechanism of thrombin-catalyzed hemostatic reactions in blood platelets. Acta Physiologica Scandinavica 56 Suppl 195
    PubMedGoogle Scholar
  • 10 Kaminer B, Kimura J. 1972; Deuterium oxide: Inhibition of calcium release in muscle. Science 176: 406
    CrossrefPubMedGoogle Scholar
  • 11 Käser-Glanzmann R, Jakábová M, George JN, Lüscher EF. 1977; Stimulation of calcium uptake in platelet membrane vesicles by adenosine 3’, 5’-cycIic monophosphate and protein kinase. Biochimica et Biophysica Acta 466: 429
    CrossrefPubMedGoogle Scholar
  • 12 Käser-Glanzmann R, Jakábová M, George JN, Lüscher EF. 1978; Further characterization of calcium-accumulating vesicles from human blood platelets. Biochimica et Biophysica Acta 512: 1
    CrossrefPubMedGoogle Scholar
  • 13 Le Breton GC, Dinerstein RJ. 1977; Effect of the calcium antagonist TMB-6 on intracellular calcium distribution associated with platelet shape change. Thrombosis Research 10: 521
    CrossrefPubMedGoogle Scholar
  • 14 Le Breton GC, Dinerstein RJ, Roth LJ, Feinberg H. 1976; a Direct evidence for intracellular divalent cation redistribution associated with platelet shape change. Biochemical and Biophysical Research Communications 71: 362
    CrossrefPubMedGoogle Scholar
  • 15 Le Breton GC, Feinberg H. 1974; ADP-induced changes in intraplatelet Ca2+ion concentration. Pharmacologist 16: 313
    PubMedGoogle Scholar
  • 16 Le Breton GC, Sandler WC, Feinberg H. 1976; b The effect of D2O and chlortetracycline on ADP-induced platelet shape change and aggregation. Thrombosis Research 8: 477
    CrossrefPubMedGoogle Scholar
  • 17 Lehninger AL, Carafoli E, Rossi CS. 1967; Energy-linked ion movements in mitochondrial systems. Advances in Enzymology 29: 259
    PubMedGoogle Scholar
  • 18 MacFarlane DE, Walsh PN, Mills DC B, Holmsen H, Day HJ. 1975; The role of thrombin in ADP-induced platelet aggregation and release. British Journal of Haematology 30: 457
    CrossrefPubMedGoogle Scholar
  • 19 MacMillan DC. 1966; Secondary clumping effect in human citrated platelet-rich plasma produced by adenosine diphosphate and adrenaline. Nature, Lond 211: 140
    CrossrefPubMedGoogle Scholar
  • 20 Malagodi MH, Chiou CY. 1974; a Pharmacological evaluation of a new Ca2+antagonist, 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8): studies in smooth muscles. European Journal of Pharmacology 27: 25
    CrossrefPubMedGoogle Scholar
  • 21 Malagodi MH, Chiou CY. 1974; b Pharmacological evaluation of a new Ca++antagonist, 8-(N,N-diethylamino)-octyl-3,4,5-trimethylbenzoate hydrochloride (TMB-8): studies in skeletal muscles. Pharmacology 12: 20
    CrossrefPubMedGoogle Scholar
  • 22 Massini P, Luscher EF. 1974; Some effects of ionophores for divalent cations on blood platelets - comparison with the effects of thrombin. Biochimica et Biophysica Acta 372: 109
    CrossrefPubMedGoogle Scholar
  • 23 Massini P, Lücher EF. 1976; On the significance of the influx of calcium ions into stimulated human blood platelets. Biochimica et Biophysica Acta 436: 652
    CrossrefPubMedGoogle Scholar
  • 24 Mills DC B, Robb IA, Roberts GC K. 1968; The release of nucleotides, 5- hydroxytryptamine and enzymes from human blood platelets during aggregation. Journal of Physiology 195: 715
    CrossrefPubMedGoogle Scholar
  • 25 Müeller-Eckardt CH, Lücher EF. 1968; Immune reactions of human blood platelets. I. A comparative study on the effects on platelets of heterologous antiplatelet antiserum, antigen- antibody complexes, and thrombin. Thrombosis et Diathesis Haemorrhagica 20: 155
    PubMedGoogle Scholar
  • 26 Mürer EH, Holme R. 1970; A study of the release of calcium from human platelets and its inhibition by metabolic inhibitors, N-ethylmaleimide and aspirin. Biochimica et Biophysica Acta 222: 197
    CrossrefPubMedGoogle Scholar
  • 27 Mustard JF, Perry DW, Kinlough-Rathbone RL, Packham MA. 1975; Factors responsible for ADP-induced release of platelet constituents. American Journal of Physiology 228: 1757
    PubMedGoogle Scholar
  • 28 Reimers HJ, Kinlough-Rathbone RL, Cazenave JP, Senyi AF, Hirsch J, Packham MA, Mustard JF. 1976; In vitro and in vivo functions of thrombin-treated platelets. Thrombosis and Haemostasis 35: 151
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Robblee LS, Shepro D, Belamarich FA. 1973; a Calcium uptake and associated adenosine triphosphatase activity of isolated platelet membranes. Journal of General Physiology 61: 462
    CrossrefPubMedGoogle Scholar
  • 30 Robblee LS, Shepro D, Belamarich FA, Towle C. 1973; b Platelet calcium flux and the release reaction. Series Haematologica 6: 311
    PubMedGoogle Scholar
  • 31 Sato T, Herman L, Chandler JA, Stracher A, Detwiler TC. 1975; Localization of a thrombin-sensitive calcium pool in platelets. Journal of Histochemistry and Cytochemistry 23: 103
    CrossrefPubMedGoogle Scholar
  • 32 Skaer RJ, Peters PD, Emmines JP. 1974; The localization of calcium and phosphorus in human platelets. Journal of Cell Science 15: 679
    PubMedGoogle Scholar
  • 33 Skaer RJ, Peters PD, Emmines JP. 1976; Platelet dense bodies: a quantitative microprobe analysis. Journal of Cell Science 20: 441
    PubMedGoogle Scholar
  • 34 Statland BE, Heaoan BM, White JG. 1969; Uptake of calcium by platelet relaxing factor. Nature, Lond 223: 521
    CrossrefPubMedGoogle Scholar
  • 35 White G. 1972; a Interaction of membrane systems in blood platelets. American Journal of Pathology 66: 295
    PubMedGoogle Scholar
  • 36 White JG. 1972; b Exocytosis of secretory organelles from blood platelets incubated with cationic polypeptides. American Journal of Pathology 69: 41
    PubMedGoogle Scholar
  • 37 Tada M, Kirchberger MA, Repke DI, Katz AM. 1974; The stimulation of calcium transport in cardiac sarcoplasmic reticulum by adenosine 3’:5’:-monophosphate-dependent protein kinase. Journal of Biological Chemistry 249: 6174
    PubMedGoogle Scholar
  • 38 Zakai N, Kulka RG, Loyter A. 1976; Fusion of human erythrocyte ghosts promoted by the combined action of calcium and phosphate ions. Nature, Lond 263: 696
    CrossrefPubMedGoogle Scholar