Summary
A quantitative analysis of myocardial Ca-metabolism was carried out on isolated, isovolumetric (10 ml/min) perfused guinea pig hearts by combined determinations of the total Ca-content and kinetics of 45Ca-efflux (collecting period 60 min) (Fig. 1). The kinetics of 45Ca-uptake was estimated by extrapolating 45Ca-efflux curves of heart muscles isotopically loaded for different times (2, 5, 10, 30 60 min) to the end of the loading-period (Fig. 2).
From the specific activity it was possible to express the absolute Ca-content of the extrapolated compartments in μM Ca/g w.w. The amount of activity in cannules and coronary vessels was estimated by dextranblue (MW about 2 millions).
The results indicate the presence of three kinetically defined phases (K1, K2, K3) of calcium movements in guinea pig heart muscle. The content of the Ca compartments under equilibrium conditions (60 min 45Ca-loading period) was found to be: K1=0.29±0.05, K2=0.56±0.09, K3=0.30±0.04 μmoles/g w.w.
The half-time of Ca movement in these compartments for 45Ca efflux is for K1 15.5±1.0 sec, for K2 2.2±0.1 min, for K3 17.9±0.9 min, and for 45Ca uptake K1<2, K23.9± 1.11.0 , K39.2± 2.51.8 min.
Total Ca content has been found to be 1.67±0.06 μmoles/g w.w. Under control conditions about 65% of total heart muscle Ca was exchangeable. Under the influence of ouabain (1.5·10−7 M) Ca of the heart muscle exchanged to about 100%. This was caused by an increase in Ca content of compartment K3 to 0.46±0.06 μmoles/g w.w. and a significant decrease in total Ca-content to 1.32±0.07 μmoles/g w.w. The rate of 45Ca-exchange was not influenced by ouabain. The value of Ca-turnover for Ca-availability in contraction cycle and the mechanism of ouabain action are discussed.
Similar content being viewed by others
Literatur
Alpermann, H. G., Gerber, H. G., Klaus, W., Krebs, R.: Über die Beeinflussung der Ca-Aufnahme in Lipoidextrakte aus Mikrosomen und Mitochondrien des Herzens durch Digitoxigenin. Experientia (Basel) 26, 285–286 (1970)
Bailey, L. E., Dresel, P. E.: Correlation of contractile force with a calcium pool in the isolated cat heart. J. gen. Physiol. 52, 969–982 (1968)
Bailey, L. E., Sures, H. A.: The effect of ouabain on the washout and uptake of calcium in the isolated cat heart. J. Pharmacol. exp. Ther. 178, 259–270 (1971)
Cuthbert, A. W.: Membrane lipids and drug action. Pharmacol. Rev. 19, 59–105 (1967)
Dransfeld, H., Greeff, K., Schorn, A., Ting, B. T.: Calcium uptake in mitochondria and vesicles of heart and skeletal muscle in presence of potassium, sodium, k-strophanthin and pentobarbital. Biochem. Pharmacol. 18, 1335–1345 (1969)
Glitsch, H. G., Reuter, H., Scholz, H.: The effect of the internal sodium concentration on calcium fluxes in isolated guinea-pig auricles. J. Physiol. (Lond.) 209, 25–43 (1970)
Govier, W. C., Holland, W. C.: The relationship between atrial contractions and the effect of ouabain on contractile strength and calcium exchange in rabbit atria. J. Pharmacol. exp. Ther. 148, 284–289 (1965)
Greeff, K.: Zur Pharmakologie der herzwirksamen Glykoside. Klin. Physiol. 1, 340–370 (1963)
Grossman, A., Furchgott, R. E.: The effects of various drugs on calcium exchange in the isolated guinea-pig left auricle. J. Pharmacol. exp. Ther. 145, 162–172 (1964)
v. Hattingberg, H. M., Klaus, W., Lüllmann, H., Zepf, S.: Fluorometrische Bestimmung von Mikromengen Calcium im Muskelgewebe. Experientia (Basel) 22, 553–555 (1966)
Heinen, E., Noack, E.: Effects of k-Strophanthin and Digitoxigenin on contractile force, calcium content and exchange in guinea-pig isolated atria. Naunyn-Schmiedeberg's Arch. Pharmacol. 275, 359–371 (1972)
Holland, W. C., Sekul, A.: Influence of K+ and Ca++ on the effect of ouabain on Ca45 entry and contracture in rabbit atria. J. Pharmacol. exp. Ther. 133, 288–294 (1961)
Klaus, W.: Der Elektrolytstoffwechsel von Hirngewebe und seine Beeinflussung durch Narkotica. In: Anaesthesiologie und Wiederbelebung, Vol. 11, p. 68. Berlin-Heidelberg-New York: Springer 1967a
Klaus, W.: Comments on the role of cellular calcium in digitalis action. In: Factors influencing myocardial contractility. Edit. R. D. Tanz, F. Kavaler, and J. Robert, pp. 533–540. New York: Academic Press 1967b
Klaus, W., Alpermann, H. G., Gerber, H. G., Krebs, R.: In vitro-Untersuchungen über den Einfluß von Digitoxin auf die Aufnahme von Calcium in Lipidextrakte aus dem Herzmuskel. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 263, 230 (1968b)
Klaus, W., Krebs, R., Fleck, W.: Eine verbesserte Methode zur gleichzeitigen Messung des Sauerstoffverbrauches und der mechanischen Aktivität isolierter Muskelpräparate. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 261, 93–101 (1968a)
Klaus, W., Kuschinsky, G.: Über die Wirkung von Digitoxigenin auf den cellulären Calciumumsatz im Herzmuskelgewebe. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 244, 237–253 (1962)
Klaus, W., Lee, K. S.: Influence of cardiac glycosides on calcium binding in muscle subcellular components. J. Pharmacol. exp. Ther. 166, 68–76 (1969)
Krebs, R.: Über einige zelluläre Grundlagen der positiv inotropen Wirkung von Herzglykosiden, Katecholaminen und Methylxanthinen. Hippokrates 41, 354–365 (1970)
Krebs, R., Klaus, W., Menz, Ch.: Kompartment-Analyse des Ca-Umsatzes im isolierten Meerschweinchenherzen. Naunyn-Schmiedebergs Arch. Pharmak. 266, 377–378 (1970)
Langer, G. A.: Kinetic studies of calcium distribution in ventricular muscle of the dog. Circulat. Res. 15, 393–405 (1964)
Langer, G. A.: Ion fluxes in cardiac excitation and contraction and their relation to myocardial contractility. Physiol. Rev. 48, 708–757 (1968)
Langer, G. A., Brady, A. J.: Calcium flux in the mammalian ventricular myocardium. J. gen. Physiol. 46, 703–719 (1963)
Langer, G. A., Serena, S. D.: Relationship of calcium exchange to changes in length, tension, and work in heart muscle. Amer. J. Physiol. 213, 1125–1130 (1967)
Lee, K. S., Klaus, W.: The subcellular basis for the mechanism of inotropic action of cardiac glycosides. Pharmacol. Rev. 23, 193–261 (1971)
Lüllmann, H., Holland, W. C.: Influence of ouabain on an exchangeable calcium fraction, contractile force, and resting tension of guinea-pig atria. J. Pharmacol. exp. Ther. 137, 186–192 (1962)
Nayler, W. G.: Ca++ exchange in cardiac muscle: a basic mechanism of drug action. Amer. Heart. J. 73, 379–394 (1967)
Niedergerke, R.: The rate of action of Ca ions on the contraction of the heart. J. Physiol. (Lond.) 158, 506–515 (1957)
Niedergerke, R.: Movements of Ca in frog heart ventricles at rest and during contractions. J. Physiol. (Lond.) 167, 515–550 (1963)
Palmer, R. F., Posey, V. A.: Ion effects on calcium accumulation by cardiac sarcoplasmic reticulum. J. gen. Physiol. 50, 2085–2095 (1967)
Rescigno, A., Segre, G.: La cinetica dei farmaci e dei traccianti radioattivi. Torino: P. Boringhieri 1961
Reuter, H.: Über die Wirkung von Adrenalin auf den cellulären Ca-Umsatz des Meerschweinchenvorhofes. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 251, 401–412 (1965)
Reuter, H.: Strom-Spannungsbeziehungen von Purkinje-Fasern bei verschiedenen extracellulären Ca-Konzentrationen und unter Adrenalineinwirkung. Pflügers Arch. 287, 357–367 (1966)
Reuter, H.: The dependence of slow inward current in Purkinje-fibres on the extracellular calcium-concentration. J. Physiol. (Lond.) 192, 479–492 (1967)
Reuter, H., Seitz, N.: The dependence of Ca efflux from cardiac muscle on temperature and external ion composition. J. Physiol. (Lond.) 195, 451–470 (1967)
Reuter, H., Wollert, U.: Über die Wirkung verschiedener sympathomimetischer Amine auf Kontraktionskraft und 45Ca-Aufnahme isolierter Meerschweinchenvorhöfe. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 258, 288–296 (1967)
Sabatini-Smith, S., Holland, W. C.: Effects of temperature and ouabain on the rate of action of calcium on atrial contractions. J. Pharmacol. exp. Ther. 158, 22–27 (1967)
Scholz, H.: Elektrophysiologische und Isotopen-Versuche zur positiv inotropen Wirkung von Theophyllin, Adrenalin und Digitoxigenin am Warmblüterherzen. Habil.-Schrift, Mainz 1970
Shelburne, J. C., Serena, S. D., Langer, G. A.: The rate tension staircase in rabbit ventricular muscle: relation to ionic exchange. Amer. J. Physiol. 213, 1115–1124 (1967)
Solomon, A. K.: Compartmental methods of kinetic analysis. In: Mineral metabolism, Edit. C. L. Comar and F. Dronner, sec. A, vol. 1, pp. 119–167. New York: Academic Press 1960
Teiger, D. G., Farah, A.: Ca movements in resting and stimulated isolated rabbit atria. J. Pharmacol. exp. Ther. 157, 8–18 (1967)
Winegrad, S., Shanes, A. M.: Ca flux and contractility in guinea pig atria. J. gen. Physiol. 45, 371–394 (1962)
Wood, E. H., Heppner, R. I., Weidmann, S.: Inotropic effects of electric currents. Circulat. Res. 24, 409–445 (1969)
Author information
Authors and Affiliations
Additional information
Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.
Ein Teil der Ergebnisse wurde anläßlich der Frühjahrstagung der Deutschen Pharmakologischen Gesellschaft im Mainz mitgeteilt (Krebs et al., 1970).
Rights and permissions
About this article
Cite this article
Klaus, W., Krebs, R. Kinetische Analyse der Calcium-Kompartimente im Meerschweinchenherzen unter Kontrollbedingungen und Strophanthineinwirkung. Naunyn-Schmiedeberg's Arch. Pharmacol. 283, 277–292 (1974). https://doi.org/10.1007/BF00499188
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00499188