Skip to main content
Log in

Positive inotropic and chronotropic effects of the calcium ionophore A23187 (calimycin) on guinea-pig atria

  • Original Contributions
  • Published:
Basic Research in Cardiology Aims and scope Submit manuscript

Summary

The inotropic and chronotropic effects of the calcium ionophore A23187 (calimycin=CA) in isolated, superfused, electrically driven, auxotonically contracting left and spontaneously beating right guinea-pig atria were examined at different Ca2+ concentrations. 10−6 to 10−5 mol/l CA shows significantly positive inotropic and chronotropic effects. The inotropic effect of CA can be significantly diminished by relatively high concentrations of Ca2+ channel antagonists and relatively low concentrations of ryanodine. The positive chronotropic effect of CA can be reduced slightly, but significantly, by beta-adrenoceptor antagonists and histamine H2-receptor antagonists. From this we infer that the positive inotropic effect of CA is mainly due to the release of Ca2+ from cardiac sarcoplasmic reticulum, whereas catecholamine and histamine release appear to contribute to the positive chronotropic effect of the ionophore.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Bers DM (1985) Calcium influx and sarcoplasmic reticulum calcium release in cardiac muscle activation during postrest recovery. Am J Physiol 248:H366–381

    PubMed  Google Scholar 

  2. Clark MA, Littlejohn D, Mong S, Crooke ST (1986) Effect of leukotrienes, bradykinin and calcium ionophore (A23187) on bovine endothelial cells: release of prostacylin. Prostaglandins 31:157–166

    Article  PubMed  Google Scholar 

  3. Entman ML, Allen JC, Bornet EP, Gilette PC, Wallick ET, Schwartz A (1972) Mechanisms of calcium accumulation and transport in cardiac relaxing system (sarcoplasmic reticulum membranes): effects of verapamil, D600, X537A, and A23187. J Mol Cell Cardiol 4:681–687

    Article  PubMed  Google Scholar 

  4. Fabiato A (1985) Effects of ryanodine in skinned cardiac cells. Fed Proc 44:2970–2976

    PubMed  Google Scholar 

  5. Frank M, Sleator W (1975) Effect of ryanodine on myocardial calcium. Naynyn-Schmiedeberg's Arch Pharmacol 290:35–47

    Article  Google Scholar 

  6. Gerritsen ME, Ngancle DM, Rodrigues AM (1987) A23187-stimulated and arachidonic acid stimulated prostaglandin release from microvascular endothelial cells — effects of calcium antagonists and calmodulin inhibitors. J Pharmacol Exp Ther 240:837–846

    PubMed  Google Scholar 

  7. Hainaut K, Desmedt JE (1974) Calcium inophore A23187 potentiates twitch and intracellular calcium release in single muscle fibers. Nature 252:407–408

    PubMed  Google Scholar 

  8. Hilgemann DW, Delay MJ, Langer GA (1983) Activation-dependent cumulative depletions of extracellular free calcium in guinea-pig atrium measured with antipyrylazo III and tetramethylmurexide. Circ Res 53:779–793

    PubMed  Google Scholar 

  9. Holland DR, Steinberg MJ, Armstrong WD (1975) A23187: a calcium ionophore that directly increases cardiac contractility. Proc Soc Exp Biol Med 148:1141–1145

    PubMed  Google Scholar 

  10. Holland DR, Armstrong WD, Steinberg MJ (1978) Calcium fluxes and contractility in isolated guinea-pig atrium: effect of A23187. Am J Physiol 235:C13–19

    PubMed  Google Scholar 

  11. Hunter DR, Haworth RA, Berkoff HA (1983) Modulation of cellular calcium stores in the perfused rat heart by isoproterenol and ryanodine. Circ Res 53:703–712

    PubMed  Google Scholar 

  12. Itoh T, Kanmura Y, Kuriyama H (1985) A23187 increases Ca2+ permeability of store sites more than of surface membranes in the rabbit mesenteric artery. J Physiol 359:467–484

    PubMed  Google Scholar 

  13. Kondo N (1986) Electromechanical effects of A23187 on guinea-pig ventricular muscle: a dual action of A23187. J Mol Cell Cardiol 18:907–915

    PubMed  Google Scholar 

  14. Leuchtner J, Menzel D, Takats I, Szekeres L, Siess M (1984) Positive ino- and chronotropic effects of prostanoids on isolated atria of guinea-pigs. IUPHAR 9th Int Congr Pharmacol. London, p 37P

  15. Lindemann JP, Besch HR, Watanabe AM (1979) Indiret and direct effects of the divalent cation ionophore A23187 on guinea-pig and rat ventricular myocardium. Circ Res 44:472–482

    PubMed  Google Scholar 

  16. Malaisse WJ, Somers G, Valverde J, Couturier E (1981) Organic calcium-antagonists and calciumionophores. Drug Res 31:628–633

    Google Scholar 

  17. Mensing HJ (1977) Die Badmethode für isolierte Muskelpräparate: Beiträge zu ihrer Geschichte und zur Weiterentwicklung für Untersuchungen am Herzmuskel. Medizinische Dissertation, Universität Tübingen, FRG

    Google Scholar 

  18. Murray JJ, Dobson JG, Reed PW (1985) Effect of divalent cation ionophore A23187 on cardiac contractile parameters. Am J Physiol 249:H1195–1203

    PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  20. Pressman BC, Fahim M (1982) Pharmacology and toxicology of the monovalent carboxylic ionophores. Annu Rev Pharmacol Toxicol 22:465–490

    Article  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  22. Reuter H (1979) Properties of the two inward membrane currents in the heart. Annu Rev Physiol 41:413–424

    PubMed  Google Scholar 

  23. Shuntoh H, Tanaka C (1986) Activation of protein kinase C potentiates norepinephrine release from sinus node. Am J Physiol 251:C833–840

    PubMed  Google Scholar 

  24. Tanizaki Y, Akagi K, Lee KN, Townley RG (1983) Inhibitory effect of nifedipine and cromolyn sodium on skin reactions and45Ca uptake and histamine release in rat mast cells induced by various stimulating agents. Intern Arch Allergy Appl Immunol 72:102–109

    Google Scholar 

  25. Tiffert T, Lew VL (1986) Effect of changes in the rate of ionophore A23187-induced calcium influx on the pump-leak steady-state distribution of calcium in inosine-fed human red cells. Biochim Biophys Acta 860:429–433

    PubMed  Google Scholar 

  26. Van de Velde VJS, Van den Bossche RM, Bult H, Herman AG (1986) Modulation of prostacyclin biosynthesis by calcium entry blockers and extracellular calcium. Biochem Pharmacol 35:253–256

    Article  PubMed  Google Scholar 

  27. Waterhouse AL, Pessah JN, Francini AO, Casida JE (1987) Structural aspects of ryanodine action and selectivity. J Med Chem 30:710–716

    Article  PubMed  Google Scholar 

  28. Whiting JA, Barritt GJ (1982) On the mechanism by which hormones induce the release of Ca2+ from mitochondria in the liver cell. Biochem J 206:121–129

    PubMed  Google Scholar 

  29. Wier WG, Yue DT, Marban E (1985) Effects of ryanodine on intracellular Ca2+ transients in mammalian cardiac muscle. Fed Proc 44:2989–2993

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Preliminary results were presented at the 28th Spring Meeting of the “Deutsche Gesellschaft für Pharmakologie und Toxikologie”, March 10–13, 1987, Mainz, and at the “Herbsttagung der Deutschen Gesellschaft für Herz- und Kreislaufforschung”, October 8–10, 1987, Freiburg.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Himmel, H.M., Siess, M. Positive inotropic and chronotropic effects of the calcium ionophore A23187 (calimycin) on guinea-pig atria. Basic Res Cardiol 83, 167–175 (1988). https://doi.org/10.1007/BF01907271

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01907271

Key words

Navigation