Platelet Membrane Electrical Potential

Its Regulation and Relationship to Platelet Activation
  • Avner Rotman


The electrical potential across the platelet plasma membrane changes in response to specific stimuli (e.g., thrombin, ADP) and, conversely, alteration of the trans-membrane potential affects the platelet sensitivity to these activating agents. These electrical changes are mediated by a redistribution of cations across the plasma membrane, and therefore it may be assumed that conformational changes of membrane proteins are involved in this membrane transport process. Therefore, even though a discussion of platelet membrane potential cannot yet be related to the membrane glycoproteins, an understanding of this phenomenon is essential for a complete description of platelet membrane structure and function.


Human Platelet Blood Platelet Dense Granule Platelet Membrane Plasma Membrane Vesicle 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Addanski, S., Cahill, R. O., and Sotos, J. F., 1968, Determination of intramitochondrial pH and intramitochondrial-extramitochondrial pH gradient of isolated heart mitochondria by use of 5,5-dimethyl-2,4-oxazolidine dione, J. Biol. Chem. 243:2337–2348.Google Scholar
  2. Bamburger, E., Rottenberg, H., and Avron, M., 1973, Internal pH, pH and the kinetics of electron transport in chloroplasts, Eur. J. Biochem. 34:557–563.CrossRefGoogle Scholar
  3. Bennett, J. S., and Vilaire, G., 1979, Exposure of platelet fibrinogen receptors by ADP and epinephrine, J. Clin. Invest. 64:1393–1401.PubMedCrossRefGoogle Scholar
  4. Bentley, P. J., 1968, Amiloride: A potent inhibitor of sodium transport across the toad bladder, J. Physiol. 195:317–330.PubMedGoogle Scholar
  5. Born, G. V. R., 1970, Observations on the change in shape of blood platelets brought about by adenosine diphosphate, J. Physiol. 209:487–511.PubMedGoogle Scholar
  6. Bramhall, J. S., Morgan, J. I., Ferris, A. D., and Britten, A. Z., 1976, The use of a fluorescent probe to monitor alterations in transmembrane potentials in a single cell suspensions, Biochem. Biophys. Res. Commun. 72:654–662.PubMedCrossRefGoogle Scholar
  7. Brass, L. P., and Shattil, S. J., 1982, Changes in surface-bound and exchangeable calcium during platelet activation, J. Biol. Chem. 257:14000–14005.PubMedGoogle Scholar
  8. Brass, L. F., and Shatill, S. J., 1984, Identification and function of the high-affinity binding sites for Ca2+ on the surface of platelets, J. Clin. Invest. 73:626–632.PubMedCrossRefGoogle Scholar
  9. Buckingham, S., and Maynert, E. W., 1964, The release of 5-hydroxytryptamine, potassium and ami- noacids from platelets, J. Pharmacol. Exp. Ther. 143:332–339.PubMedGoogle Scholar
  10. Carey, P., Menashi, S., and Crawford, N., 1982, Localization of cyclooxygenase and thromboxane synthetase in human platelet intracellular membrane, Biochem. J. 204:847–851.PubMedGoogle Scholar
  11. Carty, S. E., Johnson, R. G., and Scarpa, A., 1981, Serotonin transport in isolated platelet granules, J. Biol. Chem. 256:11244–11250.PubMedGoogle Scholar
  12. Cooley, M. H., and Cohen, P., 1967, Potassium transport in human blood platelets, J. Lab. Clin. Med. 70:69–79.PubMedGoogle Scholar
  13. Costa, J. L., and Murphy, D. L., 1980, Unique specializations for the subcellular compartmentalization of amines in pig and human platelets, in: Platelets: Cellular Response Mechanisms and their Biological Significance (A. Rotman, F. A. Meyer, C. Gitler, and A. Silberg, eds.), Wiley, Chichester, pp. 233–247.Google Scholar
  14. Cuthberg, A. W., and Shum, W. K., 1974, Amiloride and the sodium channel. Arch. Pharmacol. 281:261- 269.Google Scholar
  15. Cutler, L., Rodan, G., and Feinstein, M. B., 1978, Cytochemical localization of adenylate cyclase and of calcium ion, magnesium ion-activated ATPase in the dense tubular system of human blood platelets, Biochim. Biophys. Acta 542:357–371.PubMedCrossRefGoogle Scholar
  16. Deamer, D. W., Prince, R., and Crofts, A., 1972, The response of fluorescent amines to gradients across liposome membranes, Biochim. Biophys. Acta 274:323–335.PubMedCrossRefGoogle Scholar
  17. Detwiler, T. L., Caro, I. F., and Feinman, R. D., 1978, Evidence that calcium regulates platelet function, Thromb. Haemostasis 40:207–211.Google Scholar
  18. Feinberg, H., Michel, H., and Bom, G. V. R., 1974, Determination of the fluid volume of platelets by their separation through silicon oil, J. Lab. Clin. Med. 84:926–934.Google Scholar
  19. Feinberg, H., Sandler, W. C., Scorer, M., Le Breton, G. C., Grossman, B., and Bom, G. V. R., 1977, Movement of sodium in human platelets induced by ADP, Biochim. Biophys. Acta 470:317–324.PubMedCrossRefGoogle Scholar
  20. Feinstein, M. B., Henderson, E. G., and Sha'afi, R. I., 1977, The effects of alterations of transmembrane Na+ and K+ gradients by ionophores (nigericin, monensin) on serotonin transport in human blood platelets, Biochim. Biophys. Acta 468:284–295.PubMedCrossRefGoogle Scholar
  21. Fishkes, H., and Rudnick, G., 1982, Bioenergetics of serotonin transport by membrane vesicles derived from platelet dense granules, J. Biol. Chem. 257:5671–5677.PubMedGoogle Scholar
  22. Friedhoff, L. T., and Sonenberg, M., 1981, The effect of altered transmembrane ion gradients on membrane potential and aggregation of human platelets in blood plasma, Biochem. Biophys. Res. Commun. 102:832–837.PubMedCrossRefGoogle Scholar
  23. Friedhoff, L. T., and Sonenberg, M., 1983, The membrane potential of human platelets, Blood 61:180–185.PubMedGoogle Scholar
  24. Fujimura, K., and Phillips, D. R., 1983, Calcium cation regulation of glycoprotein Ilb-IIIa complex formation in platelet plasma membranes, J. Biol. Chem, 258:10247–10252.PubMedGoogle Scholar
  25. Gogstad, G. O., Krutnes, M. B., and Solum, N. O., 1983, Calcium-binding proteins from human platelets, Eur. J. Biochem. 133:193–199.PubMedCrossRefGoogle Scholar
  26. Gorstein, F., Carrol, H. J., and Puszkin, E., 1967, Electrolyte concentrations, potassium flux kinetic, and the metabolic dependence of potassium transport in human platelets, J. Lab. Clin. Med. 70:92–103.Google Scholar
  27. Greenberg-Seperksy, S. M., and Simons, E. R., 1984, Cation gradient dependence of the steps in thrombin stimulation of human platelets, J. Biol. Chem. 295:1502–1508.Google Scholar
  28. Greil, H., Patschek, H., and Brossmer, R., 1972, Effect of lithium and other monovalent cations on the ADP-induced platelet aggregation in human platelet-rich plasma, Febs Lett. 26:271–273.PubMedCrossRefGoogle Scholar
  29. Grinstein, S., and Furuya, W., 1982, Calmodulin binding to platelet plasma membranes. Biochim. Biophys. Acta 686:55–64.PubMedCrossRefGoogle Scholar
  30. Gripenberg, J., 1976, Inhibition by reserpine, guanethidine and Imipramine of the uptake of 5-hydroxytryp-tamine by rat peritoneal mast cells in vitro, Acta. Physiol. Scand. 96:407–416.CrossRefGoogle Scholar
  31. Hoffman, J. F., and Laris, P. C., 1974, Determination of membrane potentials in human and amphiuma red blood cells by means of a fluorescent probe, J. Physiol. 239:519–552.PubMedGoogle Scholar
  32. Home, W. C., and Simons, E. R., 1976, The effect of aggregating agents and drugs on the membrane potential of washed human platelets (abstract). Fed. Proc. 35:1451.Google Scholar
  33. Home, W. C., and Simons, E. R., 1978a, Probes of transmembrane potentials in platelets: changes in cyanine dye fluorescence in response to aggregation stimuli. Blood 51:741–749.Google Scholar
  34. Home, W. C., and Simons, E. R., 1978b, Effects of amiloride on the response of human platelets to bovine a-thrombin, Thromb. Res. 13:599–607.CrossRefGoogle Scholar
  35. Home, W. C., Norman, N. E., Schwartz, D. B., and Simons, E. R., 1981, Changes in cytoplasmic pH and in membrane potential in thrombin-stimulated human platelets, Eur. J. Biochem. 120:295–302.CrossRefGoogle Scholar
  36. Johnson, R. G., Scarpa, A., and Salganicoff, L., 1978, The internal pH of isolated serotonin-containing granules of pig platelets, J. Biol. Chem. 253:7061–7068.PubMedGoogle Scholar
  37. Johnson, R. G., Carty, S. E., Fingerhood, B. J., and Scarpa, A., 1980, The intemal pH of mast cell granules, Febs Lett. 120:75–79.PubMedCrossRefGoogle Scholar
  38. Käser-Glanzmann, R., George, J. N., Jakabova, M., and Lüscher, E. F., 1977, Stimulation of calcium uptake into platelet membrane vesicles by adenosine 3'5'-cyclic monophosphate and protein kinase, Biochim. Biophys. Acta 512:1–12.Google Scholar
  39. Käser-Glanzmann, R., Jakabova, M., George, J. N., and Lüscher, E. F., 1978, Further characterization of calcium accumulating vesicles from human blood platelets, Biochim. Biophys. Acta 512:1–12.PubMedCrossRefGoogle Scholar
  40. Keyes, S. R., and Rudnick, G., 1982, Coupling of transmembrane proton gradients to platelet serotonin transport, J. Biol. Chem. 257:1172–1176.PubMedGoogle Scholar
  41. Kinlough-Rathbone, R. L., Chahil, A., and Mustard, J. F., 1974, Divalent cations and the release reaction of pig platelets. Am. J. Physiol. 226:235–239.PubMedGoogle Scholar
  42. Kretsinger, R. H., 1979, The informational role of calcium in the cytosol, in: Advances in Cyclic Nucleotides Research (P. Greengard, and G. A. Robinson, eds.), Raven Press, New York, pp. 1–26.Google Scholar
  43. Lagarde, M., Quichardant, M., Menashi, S., and Crawford, N., 1982, The phospholipid and fatty acid composition of human platelet surface and intracellular membranes isolated by high voltage free from electrophoresis, J. Biol. Chem. 257:3100–3104.PubMedGoogle Scholar
  44. Lages, B., and Weiss, H. J., 1981, Dependence of human platelet functional response on divalent cations: Aggregation and secretion in heparin—and hirudin—anticoagulated platelet-rich plasma and the effects of chelating agents, Thromb. Haemostasis 45:173–179.Google Scholar
  45. Larsen, N. E., Home, W. C., and Simons, E. R., 1979, Platelet interaction with active and TLCK- inactivated a-thrombin, Biochem. Biophys. Res. Commun. 87:403–409.PubMedCrossRefGoogle Scholar
  46. Le Breton, G. C., and Feinberg, H., 1974, ADP-induced changes in intracellular Ca++ ion concentration. Pharmacologist 16:699.Google Scholar
  47. Le Breton, G. C., Dinerstein, R. J., Roth, L. J., and Feinberg, H., 1976, Direct evidence for intracellular divalent cation redistribution associated with platelet shape change, Biochem. Biophys, Res. Commun. 71:362–370.CrossRefGoogle Scholar
  48. Lingjarde, O., 1960, Uptake of serotonin in blood platelets: Dependence on sodium and chloride, and inhibition by choline, Febs Lett. 3:103–106.CrossRefGoogle Scholar
  49. Lüscher, E. F., Massini, P., and Käser-Glanzmann, R., 1980, The role of calcium ions in the induction of platelet activities, in:Platelets: Cellular Response Mechanisms and their Biological Significance (A. Rotman, F. A. Meyer, C. Gitler, and A. Silberberg, eds.), Wiley, Chichester, pp. 66–77.Google Scholar
  50. Maclntyre, D. E., and Gordon, J. L., 1975, Calcium-dependent stimulation of platelet aggregation by PGE2, Nature (London) 258:337–339.CrossRefGoogle Scholar
  51. Maclntyre, D. E., and Rink, T. J., 1982, The role of platelet membrane potential in the inhibition of platelet aggregation, Thromb. Haemostasis 47:22–26.Google Scholar
  52. Massini, P., and Lüscher, E. P., 1976, On the significance of the influx of calcium into stimulated human blood platelets, Biochim. Biophys. Acta 436:652–663.PubMedCrossRefGoogle Scholar
  53. Massini, P., Kaser-Glanzmann, R., and Luscher, E. P., 1978, Movement of calcium ions and their role in the activation of platelets, Thromb. Haemostasis 40:212–218.Google Scholar
  54. McDonald, V. W., and Jobsis, P. P., 1976, Spectrophotometric studies on the pH of frog skeletal muscle, J. Gen. Physiol. 68:179–195.CrossRefGoogle Scholar
  55. Menashi, S., Weintroub, H., and Crawford, N., 1981, Characterization of human platelet surface and intracellular membranes isolated by free flow electrophoresis, J. Biol. Chem. 256:4095–4101.PubMedGoogle Scholar
  56. Menashi, S., Davis, C., and Crawford, N., 1982, Calcium uptake associated with intracellular membrane fraction prepared from human blood platelets by high-voltage, free flow electrophoresis, Febs Lett. 140:298–302.PubMedCrossRefGoogle Scholar
  57. Miletich, J. P., Jackson, C. M., and Magerus, P. W., 1978, Properties of the factor Xa binding site on human platelets. J. Biol. Chem. 253:6908–6916.PubMedGoogle Scholar
  58. Modai, I., Rotman, A., Munitz, H., Tijano, S., and Wijsenbeek, H., 1979, Active uptake of serotonin by blood platelets of acute schizophrenic patients, Psychopharmacology 64:193–196.PubMedCrossRefGoogle Scholar
  59. Montecucco, D., Pozzan, T., and Rink, T. J., 1979, Dicarbocyanine fluorescent probes of membrane potential block lymphocyte capping, deplete cellular ATP and inhibit respiration of isolated mitochondria, Biochim. Biophys. Acta 552:552–557.PubMedCrossRefGoogle Scholar
  60. Murer, E. H., Hellem, A. J., and Rosenberg, M. C., 1976, Energy metabolism and platelet function, Scand. Lab. Invest. 19:280–282.CrossRefGoogle Scholar
  61. Nelson, P. J., and Rudnick, G., 1979, Coupling between platelet 5-hydroxytryptamine and potassium transport, J. Biol. Chem. 254:10084–10089.PubMedGoogle Scholar
  62. Ohkuma, S., and Poole, B., 1978, Pluorescence probes measurements of the intralysosomal pH in living cells and the perturbation of pH by various agents, Proc. Natl. Acad. Sei. U.S.A. 75:3327–3331.PubMedCrossRefGoogle Scholar
  63. Owen, N. E., and Le Breton, G. C., 1980, The involvement of calcium in epinephrine or ADP potentiation of human platelet aggregation, Thromb. Res. 17:855–863.PubMedCrossRefGoogle Scholar
  64. Peerschke, E. I., Grant, R. A., and Zucker, M. B., 1980, Decreased association of 45Calcium with platelets unable to aggregate due to thrombasthenia or prolonged calcium deprivation, Br. J. Haematol. 46:247–256.PubMedCrossRefGoogle Scholar
  65. Pick, U., and Avron, M., 1976, A method for measuring the internal pH in illuminated chloroplasts based on the stimulation of protein uptake by amines, Eur. J. Biochem. 70:569–576.PubMedCrossRefGoogle Scholar
  66. Pletscher, A., 1968, Metabolism, transfer and storage of 5-hydroxytryptamine in blood platelets, Br. J. Pharmacol. Chemother. 32:1–16.PubMedGoogle Scholar
  67. Pletscher, A., and Laubscher, A., 1980, Use and limitation of platelets as a model for neuron: Amine release and shape change reactions, in: Platelets: Cellular Response Mechanisms and their Biological Significance (A. Rotman, P. A. Meyer, C. Gitler, and A. Silberberg, eds.), Wiley, Chichester, pp. 267–276.Google Scholar
  68. Rittenhouse-Simmons, S., Russell, P. A., and Deykin, D., 1977, Mobilization of arachidonic acid in human platelets kinetics and Ca++ dependency, Biochim. Biophys. Acta 488:370–380.PubMedGoogle Scholar
  69. Robblee, L. S., and Shepro, D., 1976, The effect of external calcium and lanthanum on platelet calcium content and on the release reaction, Biochim. Biophys. Acta 436:448–459.PubMedCrossRefGoogle Scholar
  70. Rotman, A., 1980, The use of blood platelets serotonin uptake as a model in the study of mental illness, in: Enzymes and Neurotransmitters in Mental Disease (E. Esdin, T. S. Sourkes, and M. B. H. Youdim, eds.), Wiley, Chichester, pp. 65–76.Google Scholar
  71. Rotman, A., 1983, Blood platelets in psychopharmacological research, Prog. Neuropsychopharmacol. 7:135–151.CrossRefGoogle Scholar
  72. Rotman, A., and Heldman, J., 1980, Azidofluorescein diacetate: A novel intracellular labelling reagent, Febs Lett. 122:215–218.PubMedCrossRefGoogle Scholar
  73. Rotman, A., and Heldman, J., 1982, Measurement of the intracellular pH of blood platelets using a photolabel fluorescent probe, Biochim. Biophys. Acta 720:75–80.PubMedCrossRefGoogle Scholar
  74. Rotman, A., Modai, L, Munitz, H., and Wijsejibeek, H., 1979, Active uptake of serotonin by blood platelets of schizophrenic patients, Febs Lett. 101:134–136.PubMedCrossRefGoogle Scholar
  75. Rotman, A., Caplan, R., and Szekely, G. A., 1980, Platelet uptake of serotonin in autistic and other psychotic children, Psychopharmacology 65:245–248.CrossRefGoogle Scholar
  76. Rotman, A., Zemishlany, Z., Munitz, H., and Wijsenbeek, H., 1982, The active uptake of serotonin by platelets of schizophrenic patients and their families: Possibility of a genetic marker, Psychopharmacology 77:171–174.PubMedCrossRefGoogle Scholar
  77. Rudnick, G., 1977, Active transport of 5-hydroxytryptamine by plasma membrane vesicles isolated from human blood platelets, J. Biol. Chem. 252:2170–2174.PubMedGoogle Scholar
  78. Rudnick, G., and Nelson, P. J., 1978, Platelet 5-hydroxytryptamine transport, an electroneutral mechanism coupled to potassium. Biochemistry 17:4739–4742.PubMedCrossRefGoogle Scholar
  79. Sandler, W. C., Le Breton, G. C., and Feinberg, H., 1980, Movement of sodium into human platelets, Biochim. Biophys. Acta 600:448–455.PubMedCrossRefGoogle Scholar
  80. Schuldiner, S., Rottenberg, H., and Avron, M., 1972, Determination of pH in chloroplasts. 2. Fluorescent amines as a probe for the determination of pH in chloroplasts, Eur. J. Biochem. 25:64–70.PubMedCrossRefGoogle Scholar
  81. Sims, P. J., Waggoner, A. S., Wang, C. H., and Hoffman, J. F., 1974, Studies on the mechanism by which cyanine dyes measure membrane potential in red blood cells and phosphatidylcholine vesicles. Biochemistry 13:3315–3330.PubMedCrossRefGoogle Scholar
  82. Skaer, R. J., Peters, P. D., and Emmines, J. P., 1974, The localization of calcium and phosphorus in human platelets, Cell Sci. 15:679–692.Google Scholar
  83. Sneddon, J. M., 1971, Relationship between internal Na+/K+ and the accumulation of 14C-5-hydroxytryp-tamine by rat platelets, Br. J. Pharmacol 43:834–844.PubMedGoogle Scholar
  84. Strittmatter, W. J., Davis, J. N., and Lefkowitz, R., 1977, Alpha-adrenegic receptors in rat parotid cells. Desensitization of receptor binding sites and potassium release, J. Biol. Chem. 252:5478–5482.PubMedGoogle Scholar
  85. Thomas, J. A., and Johnson, D. L., 1975, Fluorescein conjugates of cytochrome c as internal pH probes in submitochondrial particles, Biochem. Biophys. Res. Commun. 65:931–939.PubMedCrossRefGoogle Scholar
  86. Thomas, J. A., Buchsbaum, R. N., Zimnial, A., and Racker, E., 1979, Intracellular pH measurements in Ehrlich ascites tumor cells utilizing spectroscopic probes generated in situ, Biochemistry 18:2210–2218.PubMedCrossRefGoogle Scholar
  87. Tranzer, J. P., DaPrada, M., and Pletscher, A., 1966, Ultrastructural localization of 5-hydroxytryptamine in blood platelets. Nature (London) 212:1574–1575.CrossRefGoogle Scholar
  88. Tuomisto, J., and Tukiainen, E., 1976, Decreased uptake of 5-hydroxytryptamine in blood platelets from depressed patients. Nature (London) 262:596–598.CrossRefGoogle Scholar
  89. Tuomisto, J., Tukiainen, E., and Ahlfors, U. G., 1979, Decreased uptake of 5-hydroxytryptamine in blood platelets from patients with endogenous depression, Psychopharmacology 65: 141–141.PubMedCrossRefGoogle Scholar
  90. Varecka, L., Kovac, L., and Pogady, J., 1978, Trypsin and calcium ions elicit changes in the membrane potential in pig blood platelets, Biochem. Biophys. Res. Commun. 85:1233–1238.PubMedCrossRefGoogle Scholar
  91. Wagner, H. R., and Davis, J. N., 1979, Beta-adrenergetic receptor regulation by agonist and membrane depolarization in rat slices. Proc. Natl. Acad. Sei. U.S.A. 76:2057–2066.PubMedCrossRefGoogle Scholar
  92. White, J. G., 1972a, Interaction of membrane systems in blood platelets, Am. J. Pathol. 66:295–372.Google Scholar
  93. White, J. G., 1972b, The sarcoplasmic reticulum of platelets, Fed Proc. 31:654.Google Scholar
  94. Wiley, J. S., Kuchibhotla, J., Shaller, C. C., and Colman, R. W., 1976, Potassium uptake and release by human blood platelets, Blood 48:185–197.PubMedGoogle Scholar
  95. Wilkins, J. A., and Salganicoff, L., 1981, Participation of a transmembrane proton gradient in 5-hydroxytryptamine transport by platelet dense granules and dense granules ghosts, Biochem. J. 198:113- 123.Google Scholar
  96. Zieve, P. D., Gamble, J. L., and Jackson, D. P., 1964, Effects of thrombin on the potassium and ATP content of platelets, J. Clin. Invest. 43:2063–2069.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Avner Rotman
    • 1
  1. 1.Department of Membrane ResearchWeizmann Institute of ScienceRehovotIsrael

Personalised recommendations