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Calcium Signaling pp 1017–1038Cite as

Role Ca2+ in Mechanisms of the Red Blood Cells Microrheological Changes

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 740))

Abstract

To assess the physiological role of intracellular Ca2+ in the changes of microrheological red blood cell (RBC) properties (RBC deformability and aggregation), we employed several types of chemicals that can increase and decrease of the intracellular Ca2+ concentration. The rise of Ca2+ influx, stimulated by mechanical loading, A23187, thrombin, prostaglandin F2α was accompanied by a moderate red cell deformability lowering and an increase of their aggregation. In contrast, Ca2+ entry blocking into the red cells by verapamil led to a significant RBC aggregation decrease and deformability rise. Similar microrheological changes were observed in the red blood cells treated with phosphodiesterase inhibitors IBMX, vinpocetine, rolipram, pentoxifylline. When forskolin (10 μM), an AC stimulator was added to RBC suspension, the RBC deformability was increased (p <0.05). Somewhat more significant deformability rise appeared after RBC incubation with dB-AMP. Red cell aggregation was significantly decreased under these conditions (p<0.01). On the whole the total data clearly show that the red cell aggregation and deformation changes were connected with an activation of both intracellular signaling pathways: Ca2+ regulatory mechanism and Gs-protein/adenylyl-cyclase-cAMP system. And the final red cell microrheological regulatory effect is connected with the crosstalk between these systems.

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References

  1. Berga L, Dolz J, Vives-Corrons JL, Feliu E, Rozman C (1984) Viscometric methods for assessing red cell deformability and fragmentation. Biorheology Suppl 1:297–301

    PubMed  CAS  Google Scholar 

  2. Nash GB, Meiselman HJ (1985) Alteration of red cell membrane viscoelasticity by heat treatment: effect on cell deformability and suspension viscosity. Biorheology 22(1):73–84

    PubMed  CAS  Google Scholar 

  3. Mohandas N, Chasis JA (1993) Red blood cell deformability, membrane material properties and shape: regulation by transmembrane, skeletal and cytosolic proteins and lipids. Semin Hematol 30(3):171–192

    PubMed  CAS  Google Scholar 

  4. Zhang J, Johnson PC, Popel AS (2008) Red blood cell aggregation and dissociation in shear flows simulated by lattice Boltzmann method. J Biomech 41:47–55

    Article  PubMed  Google Scholar 

  5. Kaliviotis E, Ivanov I, Antonova N, Yianneskis M (2010) Erythrocyte aggregation at non-steady flow conditions: a comparison of characteristics measured with electrorheology and image analysis. Clin Hemorheol Microcirc 44:43–54

    PubMed  Google Scholar 

  6. Bishop JJ, Nance PR, Popel AS, Intaglietta M, Johnson PC (2001) Effect of erythrocyte aggregation on velocity profiles in venules. Am J Physiol Heart Circ Physiol 280:H222–H236

    PubMed  CAS  Google Scholar 

  7. Minetti G, Low PS (1997) Erythrocyte signal transduction pathways and their possible functions. Curr Opin Hematol 4:116–121

    Article  PubMed  CAS  Google Scholar 

  8. Hilario S, Saldanha C, Martin-a-Silva J (1999) The effect of adrenaline upon human erythrocyte properties sex-related differences? (abstract). Biorheology 36(1–2):124

    Google Scholar 

  9. De Oliveira S, Silva-Herdade A, Saldanha C (2008) Modulation of erythrocyte deformability by PKC activity. Clin Hemorheol Microcirc 39:363–373

    PubMed  Google Scholar 

  10. De Oliveira S, Saldanha C (2010) An overview about erythrocyte membrane. Clin Hemorheol Microcirc 44:63–74

    PubMed  Google Scholar 

  11. Oonishi T, Sakashita K, Uyesaka N (1997) Regulation of red blood cell filterability by Ca2+ influx and cAMP-mediated signaling pathways. Am J Physiol 273:C1828–C1834

    PubMed  CAS  Google Scholar 

  12. Tuvia S, Moses A, Gulayev N, Levin S, Korenstein R (1999) Beta-adrenergic agonists regulate cell membrane fluctuations of human erythrocytes. J Physiol 516:781–792

    Article  PubMed  CAS  Google Scholar 

  13. Towart R, Schramm M (1985) Calcium channel modulators and calcium channels. Biochem Soc Symp 50:81–95

    PubMed  CAS  Google Scholar 

  14. Hallett MB, Campbell AK (1984) Is intracellular Ca2+ the trigger for oxygen radical production by polymorphonuclear leucocytes? Cell Calcium 5(1):1–19

    Article  PubMed  CAS  Google Scholar 

  15. Minetti G, Ciana A, Balduini C (2004) Differential sorting of tyrosine kinases and phosphotyrosine phosphatases acting on band 3 during vesiculation of human erythrocytes. Biochem J 377:489–497

    Article  PubMed  CAS  Google Scholar 

  16. Muravyov AV, Tikhomirova IA, Maimistova AA, Bulaeva SV (2010) Crosstalk between adenylyl cyclase signaling pathway and Ca2+ regulatory mechanism under red blood cell microrheological changes. Clin Hemorheol Microcirc 45:337–345

    PubMed  CAS  Google Scholar 

  17. Sauer H, Hescheler J, Wartenberg M (2000) Mechanical strain-induced Ca2+ waves are propagated via ATP release and purinergic receptor activation. Am J Physiol Cell Physiol 279:C295–C307

    PubMed  CAS  Google Scholar 

  18. Takakuwa Y, Mohandas N, Ishibashi T (1990) Regulation of red cell membrane deformability and stability by skeletal protein network. Biorheology 27(3–4):357–365

    PubMed  CAS  Google Scholar 

  19. Thiel M, Bardenheuer H (1992) Regulation of oxygen radical production of human polymorphonuclear leukocytes by adenosine: the role of calcium. Pflugers Arch 420(5–6):522–528

    Article  PubMed  CAS  Google Scholar 

  20. Del Carlo B, Pellegrini M, Pellegrino M (2003) Modulation of Ca2+-activated K+ channels of human erythrocytes by endogenous protein kinase C. Biochim Biophys Acta 1612(1):107–116

    Article  PubMed  Google Scholar 

  21. Lang F, Birka C, Myssina S, Lang KS, Lang PA, Tanneur V, Duranton C, Wieder T, Huber SM (2004) Erythrocyte ion channels in regulation of apoptosis. Adv Exp Med Biol 559:211–217

    Article  PubMed  CAS  Google Scholar 

  22. Manno S, Takakuwa Y, Mohandas N (2005) Modulation of erythrocyte membrane mechanical function by protein 4.1 phosphorylation. J Biol Chem 280(9):7581–7587

    Article  PubMed  CAS  Google Scholar 

  23. Pitter JG, Szanda G, Duchen MR et al (2005) Prostaglandin F2α potentiates the calcium dependent activation of mitochondrial metabolism in luteal cells. Cell Calcium 37:35–44

    Article  PubMed  CAS  Google Scholar 

  24. Nedrelow JH, Cianci CD, Morrow JS (2003) c-Src binds alpha II spectrin’s Src homology 3 (SH3) domain and blocks calpain susceptibility by phosphorylating Tyr1176. J Biol Chem 278(9):7735–7741

    Article  PubMed  CAS  Google Scholar 

  25. Tepperman J, Tepperman H (1987) Metabolic and endocrine physiology and introductory text. Year Book Publishers, Inc., Chicago/London

    Google Scholar 

  26. Sundquist J, Bias DS, Hogan JE (1992) The α1-adrenergic receptor in human erythrocyte membranes mediates interaction in vitro of epinephrine and thyroid hormone at the membrane Ca2+-ATPase. Cell Signal 4:795–799

    Article  PubMed  CAS  Google Scholar 

  27. Horga JF, Gisbert JJ, De Agustin C (2000) A beta-2-adrenergic receptor activates adenylate cyclase in human erythrocyte membranes at physiological calcium plasma concentrations. Blood Cells Mol Dis 26:223–228

    Article  PubMed  CAS  Google Scholar 

  28. Muravyov AV, Yakusevich VV, Maimistova AA, Chuchkanov FA, Bulaeva SV (2007) Hemorheological efficiency of drugs, targeting on intracellular phosphodiesterase activity: in vitro study. Clin Hemorheol Microcirc 24:19–23

    Google Scholar 

  29. Laszlo R, Winkler C, Wöhrl S, Laszlo S, Eick C, Schreieck J, Bosch RF (2007) Influence of verapamil on tachycardia-induced alterations of PP1 and PP2A in rabbit atrium. Exp Clin Cardiol 12(4):175–178

    PubMed  CAS  Google Scholar 

  30. Cooper DM, Brooker G (1993) Ca2+-inhibited adenylate cyclase in cardiac tissue. Trends Pharmacol Sci 14:34–35

    Article  PubMed  CAS  Google Scholar 

  31. Phillips PG, Long Lu, Wilkins MR, Morrell NW (2005) cAMP phosphodiesterase inhibitors potentiate effects of prostacyclin analogs in hypoxic pulmonary vascular remodeling. Am J Physiol Lung Cell Mol Physiol 288:L103–L115

    Article  PubMed  CAS  Google Scholar 

  32. Romero PJ, Romero EA (2003) New vanadate-induced Ca2+ pathway in human red cells. Cell Biol Int 27(11):903–912

    Article  PubMed  CAS  Google Scholar 

  33. Singh RA, Sodhi A (1998) Expression and activation of lyn in macrophages treated in vitro with cisplatin: regulation by kinases, phosphatases and Ca2+/calmodulin. Biochim Biophys Acta 21:171–179

    Article  Google Scholar 

  34. Tong W, Zhang J, Lodish HF (2005) Lnk inhibits erythropoiesis and Epo-dependent JAK2 activation and downstream signaling pathways. Blood 15:4604–4612

    Article  Google Scholar 

  35. Neu B, Meiselman HJ (2007) Red blood cell aggregation. In: Baskurt OK, Hardeman MR, Rampling MW, Meiselman HJ (eds) Handbook of hemorheology and hemodynamics. Ios Press, Amsterdam/Berlin/Tokyo/Washington, DC, pp 114–136

    Google Scholar 

  36. Kim S, Popel AS, Intaglietta M, Johnson PC (2005) Aggregate formation of erythrocytes in postcapillary venules. Am J Physiol Heart Circ Physiol 288:H584–H590

    Article  PubMed  CAS  Google Scholar 

  37. Baskurt OK, Meiselman HJ (2007) Hemodynamic effects of red blood cell aggregation. Indian J Exp Biol 45:25–31

    PubMed  CAS  Google Scholar 

  38. Toth K, Bogar L, Juricskay I, Kelti M et al (1997) The effect of RheothRx Injection on the hemorheological parameters in patients with acute myocardial infarction. Clin Hemorheol Microcirc 17:117–125

    PubMed  CAS  Google Scholar 

  39. Rainer C, Norris S, Haywood LJ, Meiselman HJ (1989) Blood rheology and RBC aggregation in patients with angina pectoris and a prior history of myocardial infarction. Clin Hemorheol 9:923–934

    Google Scholar 

  40. Fisher M, Meiselman HJ (1991) Hemorheological factors in cerebral ischemia. Stroke 22:1164–1169

    Article  PubMed  CAS  Google Scholar 

  41. Hein HJ, Bauersachs RM, Feinstein E, Meiselman HJ (1988) Hemorheological abnormalities in chronic renal failure. Clin Hemorheol 8:425–431

    Google Scholar 

  42. Chong-Martinez B, Buchanan TA, Wenby RB, Meiselman HJ (2003) Decreased red blood cell aggregation subsequent to improved glycemic control in type 2 diabetes mellitus. Diabet Med 20:301–306

    Article  PubMed  CAS  Google Scholar 

  43. Fisher M, Giannotta S, Meiselman HJ (1987) Hemorheological alterations in patients with subarachnoid hemorrhage. Clin Hemorheol 7:611–618

    Google Scholar 

  44. Kim A, Dadgostar H, Holland GN, Wenby R et al (2006) Hemorheologic abnormalities associated with HIV infection: altered erythrocyte aggregation and deformability. Invest Ophthalmol Vis Sci 47:3927–3932

    Article  PubMed  Google Scholar 

  45. Lee BK, Durairaj A, Mehra A, Wenby RB et al (2008) Microcirculatory dysfunction in cardiac syndrome X: role of abnormal blood rheology. Microcirculation 15:451–460

    Article  PubMed  CAS  Google Scholar 

  46. Meiselman HJ (2009) RBC aggregation: 45 years being curious. Biorheology 46:1–19

    PubMed  CAS  Google Scholar 

  47. Mohandas N, Gallagher P (2008) Red cell membrane: past, present, and future. Blood 112(10):3939–3948

    Article  PubMed  CAS  Google Scholar 

  48. Sprague RS, Stephenson AH, Ellsworth ML (2007) Red not dead: signaling in and from. Trends Endocrinol Metab 18(9):350–355

    Article  PubMed  CAS  Google Scholar 

  49. Ellsworth ML, Ellis CG, Goldman D, Stephenson AH, Dietrich HH, Sprague RS (2009) Erythrocytes: oxygen sensors and modulators of vascular tone. Physiology 24:107–116

    Article  PubMed  CAS  Google Scholar 

  50. An X, Debnath G, Guo X et al (2005) Identification and functional characterization of protein 4.1R and actin-binding sites in erythrocyte beta spectrin: regulation of the interactions by phosphatidylinositol-4,5-bisphosphate. Biochemistry 44:10681–10688

    Article  PubMed  CAS  Google Scholar 

  51. Hines PS, Zen Q, Burney SN et al (2003) Novel epinephrine and cyclic cAMP – mediated action on BCAM/Lu – dependent sickle (SS) RBC adhesion. Blood 101(8):3281–3287

    Article  PubMed  CAS  Google Scholar 

  52. Bree F, Gault I P, d’Athis and Tillement JP (1984) Beta adrenoceptors of human red cells, determination of their subtypes. Biochem. Pharmacol 33:4045–4050

    Article  PubMed  CAS  Google Scholar 

  53. Sager G, Jacobsen S (1985) Effect of plasma on human erythrocyte beta-adrenergic receptors. Biochem Pharmacol 34:3767–3771

    Article  PubMed  CAS  Google Scholar 

  54. Bhattacharya S, Chakaborty PS, Basu RS et al (2001) Purification and properties of insulin-activated nitric oxide synthase from human erythrocyte membranes. Arch Physiol Biochem 109:441–449

    Article  PubMed  CAS  Google Scholar 

  55. Zancan P, Sola-Penna M (2005) Calcium influx: a possible role for insulin modulation of intracellular distribution and activity of 6-phosphofructo-1-kinase in human erythrocytes. Mol Genet Metab 86(3):392–400

    Article  PubMed  CAS  Google Scholar 

  56. Saenko EL, Yaropolov AI (1990) Studies on receptor interaction of ceruloplasmin with human red blood cells. Biochem Int 20(2):215–225

    PubMed  CAS  Google Scholar 

  57. Sakashita K, Oonishi T, Ishioka N, Uyesaka N (1999) Endothelin-1 improves the impaired filterability of red blood cells through the activation of protein kinase C. Jpn J Physiol 49:113–120

    Article  PubMed  CAS  Google Scholar 

  58. Tang LC, Schoomaker E, Wiesmann WP (1984) Cholinergic agonists stimulate calcium uptake and cGMP formation in human erythrocytes. Biochim Biophys Acta 772:235–238

    Article  PubMed  CAS  Google Scholar 

  59. Engelmann B (1991) Calcium homeostasis of human erythrocytes and its pathophysiological implications. Klin Wochenschr 69(4):137–142

    Article  PubMed  CAS  Google Scholar 

  60. Wiley JS, McCulloch KE (1982) Calcium ions, drug action and the red cell membrane. Pharmacol Ther 18(2):271–292

    Article  PubMed  CAS  Google Scholar 

  61. Romero PJ, Romero EA (1999) The role of calcium metabolism in human red blood cell ageing: a proposal. Blood Cells Mol Dis 25(1):9–19

    Article  PubMed  CAS  Google Scholar 

  62. Cicco G, Carbonara M, Stingi G, Pirrelli A (2001) Cytosolic calcium and hemorheological patterns during arterial hypertension. Clin Hemorheol 24:25–31

    CAS  Google Scholar 

  63. Ohnishi ST, Ohnishi T, Ogunmola GB (2001) Green tea extract and aged garlic extract inhibit anion transport and sickle cell dehydration in vitro. Blood Cells Mol Dis 27(1):148–157

    Article  PubMed  CAS  Google Scholar 

  64. Antonelou M, Kriebardis A, Papassideri I (2010) Aging and death signalling in mature red cells: from basic science to transfusion practice. Blood Transfus 8(3):39–47

    Google Scholar 

  65. Klarl BA, Lang PA, Kempe DS et al (2006) Protein kinase C mediates erythrocyte “programmed cell death” following glucose depletion. Am J Physiol Cell Physiol 290:C244–C253

    Article  PubMed  CAS  Google Scholar 

  66. Kaiserova K, Lakatos B, Peterajova E, Orlicky J, Varecka L (2002) Investigation of properties of the Ca2+ influx and of the Ca2+-activated K+ efflux (Gardos effect) in vanadate-treated and ATP-depleted human red blood cells. Gen Physiol Biophys 21(4):429–442

    PubMed  CAS  Google Scholar 

  67. Hoffman JF, Joiner W, Nehrke K et al (2003) The hSK4 (KCNN4) isoform is the Ca2+-activated K+ channel (Gardos channel) in human red blood cells. Proc Natl Acad Sci USA 100:7366–7371

    Article  PubMed  CAS  Google Scholar 

  68. Christophersen P, Bennekou P (1991) Evidence for a voltage-gated, non-selective cation channel in the human red cell membrane. Biochim Biophys Acta 1065:103–106

    Article  PubMed  CAS  Google Scholar 

  69. Creighton JR, Cooper DMN, Stevens T (2003) Coordinate regulation of membrane cAMP by Ca2+-inhibited adenylyl cyclase and phosphodiesterase activities. Am J Physiol (Lung Cell Mol Physiol) 284:L100–L107

    CAS  Google Scholar 

  70. Herzog M, Scherer EQ, Albrecht B, Rorabaugh B, Scofield MA (2002) CGRP receptors in the gerbil spiral modiolar artery mediate a sustained vasodilatation via a transient cAMP-mediated Ca2+-decreased. J Membr Biol 189:225–236

    Article  PubMed  CAS  Google Scholar 

  71. Ling E, Danilov YN, Cohen CM (1988) Modulation of red cell band 4.1 function by cAMP-dependent kinase and protein kinase C phosphorylation. J Biol Chem 15:2209–2216

    Google Scholar 

  72. Nunomura W, Takakuwa Y (2006) Regulation of protein 4.1R interactions with membrane proteins by Ca2+ and calmodulin. Front Biosci 1(11):1522–1539

    Article  Google Scholar 

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Acknowledgments

Work was supported by FSP “Research and educational personnel of innovative Russia for 2009–2013 years” and by grant of RFBR No. 09-04-00436-a

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  1. Department of Medicine and Biology, State Pedagogical University, Yaroslavl, Russia

    Alexei Muravyov & Irina Tikhomirova

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  1. Alexei Muravyov
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  2. Irina Tikhomirova
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Correspondence to Alexei Muravyov .

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  1. , Department of Clinical Sciences and Educ, Karolinska Institutet, Tulegatan 26, Stockholm, SE-118 83, Sweden

    Md. Shahidul Islam

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Muravyov, A., Tikhomirova, I. (2012). Role Ca2+ in Mechanisms of the Red Blood Cells Microrheological Changes. In: Islam, M. (eds) Calcium Signaling. Advances in Experimental Medicine and Biology, vol 740. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2888-2_47

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