Advertisement

Pflügers Archiv

, Volume 431, Issue 1, pp 84–90 | Cite as

Extracellular heparin inhibits Ca2+ transients and contraction in mammalian cardiac myocytes

  • Maria C. Garcia
  • Jorge A. Sanchez
  • Virendra K. Sharma
  • Shey -Shing Sheu
Original Article Molecular and Cellular Physiology

Abstract

The effect of heparin on Ca2+ transients and cell shortening was studied in isolated cardiac myocytes from rat and guinea-pig ventricles. Ca2+ signals were measured with the fluorescent indicator fura-2. Heparin reversibly decreased Ca2+ transients and cell shortening in a dose-dependent manner. Half and complete blockade were obtained with 50 μg/ml and 200 μg/ml heparin, respectively. The dihydropyridine agonist BAY K 8644 (50 nM) antagonized the effects of heparin. However, Ca2+ release elicited by caffeine (10 mM) was not affected by heparin. The actions of heparin were also studied in multicellular preparations. In papillary muscle, heparin (5 mg/ml) reversibly reduced the amplitude of the plateau of the action potential and the associated peak tension. BAY K 8644 (500 nM) also antagonized these effects. It is proposed that heparin interacts with dihydropyridine-sensitive Ca2+ channels to cause a decrease of Ca2+ transients and contractility in heart.

Key words

Cardiac muscle Calcium transients Heparin Calcium channels Extracellular matrix Glycosaminoglycans Dihydropyridines Cardiomyocytes 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Adachi S, Ito H, Akimoto H, Tanaka M, Fujisaki H, Marumo F, Hiroe H (1994) Insulin-like growth factor-ll induces hypertrophy with increased expression of muscle specific genes in cultured rat cardiomyocytes. J Mol Cell Cardiol 26:789–795Google Scholar
  2. 2.
    Adams JC, Watt FM (1993) Regulation and differentiation by the extracellular matrix. Development 117:1183–1198Google Scholar
  3. 3.
    Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD (eds) (1989) Cell adhesion, cell junctions and the extracellular matrix. In: Molecular biology of the cell. Garland, New York, pp 802–823Google Scholar
  4. 4.
    Castellot JJ, Wong K, Herman B, Hoover RL, Albertini DF, Wright TC, Caaleb BL, Karnovsky MJ (1985) Binding and internalization of heparin in vascular smooth muscle cells. J Cell Physiol 124:13–20Google Scholar
  5. 5.
    Garcia MC, Sanchez JA, Sharma VK, Sheu S-S (1994) Extracellular heparin blocks contraction and Ca transients in mammalian cardiac myocytes. Biophys J 66:A92Google Scholar
  6. 6.
    Grynkiewicz GM, Poenie M, Tsien RY (1985) A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 260:3440–3450Google Scholar
  7. 7.
    Hadley RW, Lederer WJ (1992) Comparison of the effects of BAY K 8644 on cardiac Ca current and Ca channel gating current. Am J Physiol 262:H472-H477Google Scholar
  8. 8.
    Ito H, Takikawa R, Iguchi M, Hamada E, Sugimoto T, Kurachi Y (1990) Heparin uncouples the muscarinic receptors from GK protein in the atrial cell membrane of the guinea-pig heart. Pflügers Arch 417:126–128Google Scholar
  9. 9.
    Jackson RL, Busch SJ, Cardin AD (1991) Glycosaminoglycans: molecular properties, protein interactions, and role in physiological processes. Physiol Rev 71:481–539Google Scholar
  10. 10.
    Kardami ED, Spector D, Strohman RC (1988) Heparin inhibits skeletal muscle growth in vitro. Dev Biol 126:19–28Google Scholar
  11. 11.
    Knaus HG, Scheffauer F, Romanin C, Schindler HG, Glossmann H (1990) Heparin binds with high affinity to voltage-dependent L-type Ca2+ channels. J Biol Chem 265:11156–11165Google Scholar
  12. 12.
    Knaus HG, Moshammer T, Friedrich K, Kang HC, Haugland RP, Glossman H (1992) In vivo labeling of L-type Ca2+ channels by fluorescent dihydropyridines. Evidence for a functional, extracellular heparin-binding site. Proc Natl Acad Sci USA 89:3586–3590Google Scholar
  13. 13.
    Lacinova L, Cleemann L, Morad M (1993) Ca2+ channel modulating effects in mammalian cardiac myocytes. J Physiol (Lond) 465:181–201Google Scholar
  14. 14.
    Markwardt F, Nilius B (1988) Modulation of calcium channel currents in guinea-pig single ventricular heart cells by the dihydropyridine Bay K 8644. J Physiol (Lond) 399:559–575Google Scholar
  15. 15.
    Mattai J, Kwak JCT (1981) Mg and Ca binding to heparin in the presence of added univalent salt. Biochim Biophys Acta 677:303–312Google Scholar
  16. 16.
    Sheu S-S, Sharma VK, Banerjee SP (1984) Measurement of cytosolic free calcium concentration in isolated rat ventricular myocytes with quin 2. Circ Res 55:830–834Google Scholar
  17. 17.
    Soonpaa MH, Oberpriller JO, Oberpriller JC (1994) Factors altering DNA synthesis in the cardiac myocyte of the adult newt, Notophthamus viridescens. Cell Tissue Res 275:377–382Google Scholar
  18. 18.
    Steadman BW, Moore KB, Spitzer KW, Bridge JHB (1988) A video system for measuring motion in contracting heart cells. IEEE Trans Biomed Eng 35:264–272Google Scholar
  19. 19.
    Weiner HL, Swain JL (1989) Acidic fibroblast growth factor mRNA is expressed by cardiac myocytes in culture and the protein is localized to the extracellular matrix. Proc Natl Acad Sci USA 86:2683–2687Google Scholar
  20. 20.
    Worley PF, Baraban JM, Supattapone S, Wilson VS, Snyder SH (1987) Characterization of inositol triphosphate receptor binding in brain. J Biol Chem 262:12132–12136Google Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Maria C. Garcia
    • 2
  • Jorge A. Sanchez
    • 2
  • Virendra K. Sharma
    • 1
  • Shey -Shing Sheu
    • 1
  1. 1.Department of Pharmacology, School of Medicine and DentistryUniversity of RochesterRochesterUSA
  2. 2.Department of PharmacologyCentre de Investigacion y de Estudios Avanzados del I.P.N.Mexico D.F.Mexico

Personalised recommendations