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Influence of low extracellular pH upon the Ca inward current and isometric contractile force in mammalian ventricular myocardium

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Summary

In isolated papillary muscles of cats the changes in Ca inward current and isometric contractile force following a decrease of extracellular pH from 7.4 to 5.5 were studied. The Ca current was analyzed (a) by measuring the upstroke velocity of Ca-mediated action potentials and (b) in voltage clamp experiments using the double sucrose gap technique.

  1. 1.

    At a pH of 5.5 the upstroke velocity of the Ca-mediated action potential decreased to 65% of the control, while overshoot and action potential duration remained almost unchanged. Furthermore, the relative refractory period was prolonged and in some cases, a “Wenckebach-like” phenomenon occurred. In voltage clamp experiments, the slow inward current was found to be diminished to 50–60% of the initial control value and over a broad voltage range the current voltage relationship curve was shifted to weaker currents. Acidosis did not influence the steady state inactivation but altered the kinetics of inactivation of the slow inward current and induced an increase of τinactivation and τrecovery. This indicates that acidosis exerts a complex effect on the slow membrane channel.

  2. 2.

    The normal response of the Ca current towards variations of the extracellular Ca concentration (0.5–4 mM) or towards the addition of the β-stimulating compound isoproterenol (2 mg/l) was not altered by the lowered extracellular pH.

  3. 3.

    In the acid medium, isometric contractile force declined to 40% of the control value within 25 min and, thus, reacted stronger than the Ca current. This indicates that those forms of acidosis used in the present experiments caused their negative inotropic effect not exclusively via a depression of the Ca current. Rather an additional intracellular effect has to be assumed which finally leads to a reduced activity of the contractile system.

  4. 4.

    At pH 5.5 excess Ca (4mM) induced the same quantitative response of the contractile system as obtained at normal pH. In contrast, the positive-inotropic effect of 2 mg/l isoproterenol was more pronounced, whilst the sensitivity of the Ca inward current towards this β-stimulating compound remained unchanged.

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References

  • Bendixen, H. M., Lauer, M. B., Flacke, W. E.: Influence of respiratory acidosis on circulatory effect of epinephrine in dogs. Circulat. Res.13, 64–70 (1963)

    PubMed  CAS  Google Scholar 

  • Benson, E. S., Freier, E. F., Vijums, R.: Carbon dioxide dissociation curve and buffer capacity of dog heart muscle. Amer. J. Physiol.209, 941–944 (1965)

    PubMed  CAS  Google Scholar 

  • Bosteels, S., Carmeliet, E.: The components of the sodium efflux in cardiac Purkyne fibres. Pflügers Arch.336, 48–59 (1972)

    Article  PubMed  CAS  Google Scholar 

  • Brown, E. B. Jr., Goott, B.: Intracellular hydrogen ion changes and potassium movement. Amer. J. Physiol.204, 765–770 (1963)

    PubMed  CAS  Google Scholar 

  • Brown, E. B., Miller, F.: Tolerance of the dog heart to carbon dioxyde. Amer. J. Physiol.170, 550–554 (1952)

    PubMed  CAS  Google Scholar 

  • Chesnais, J. M., Coraboeuf, E., Sauviat, M. P., Vassas, J. M.: Sensitivity to H, Li and Mg ions of the slow inward sodium current in frog atrial fibres. J. mol. cell. Cardiol.7, 627–642 (1975)

    Article  PubMed  CAS  Google Scholar 

  • Drouin, H., Neumcke, B.: Specific and unspecific charges at the sodium channels of the nerve membrane. Pflügers Arch.351, 207–229 (1974)

    Article  PubMed  CAS  Google Scholar 

  • Haas, H. G., Kern, R., Einwächter, H. M.: Electrical activity and metabolism in cardiac tissue: an experimental and theoretical study. J. Membrane Biol.3, 180–209 (1970)

    Article  CAS  Google Scholar 

  • Hecht, H. H., Hutter, O. F.: Action of pH on cardiac Purkinje fibres. In: Electrophysiology of the heart, pp. 105–123. Oxford: Pergamon 1965

    Google Scholar 

  • Hill, A. V.: Influence of the external medium on the internal pH of muscle. Proc. roy. Soc. B144, 1–21 (1955)

    Article  CAS  Google Scholar 

  • Hille, B., Woodhull, A. M., Shapiro, B. I.: Negative surface charge near sodium channels of nerve: divalent ions, monovalent ions and pH. Phil. Trans. B270, 301–318 (1975)

    CAS  Google Scholar 

  • Johannson, M., Nilsson, E.: Acid-base changes and excitation-contraction coupling in rabbit myocardium. I. Effects on isometric tension development at different contraction frequencies. Acta physiol. scand.93, 295–309 (1975)

    Article  Google Scholar 

  • Kammermeier, H., Rudroff, W.: Funktion und Energiestoffwechsel des isolierten Herzens bei Variation von pH, pCO2 und HCO −3 . Pflügers Arch.334, 50–61 (1972)

    Article  PubMed  CAS  Google Scholar 

  • Kohlhardt, M., Krause, H., Kübler, M., Herdey, A.: Kinetics of inactivation and recovery of the slow inward current in the mammalian ventricular myocardium. Pflügers Arch355, 1–17 (1975)

    Article  PubMed  CAS  Google Scholar 

  • Kohlhardt, M., Wirth, K., Dudeck, J.: Über den Einfluß von metabolischer Acidose auf die Kontraktilität des isolierten Herzens. Pflügers Arch. ges. Physiol.296, 352–362 (1967)

    Article  CAS  Google Scholar 

  • Lorkovic, H.: Influence of changes in pH on the mechanical activity of cardiac muscle. Circulat. Res.19, 711–720 (1966)

    PubMed  CAS  Google Scholar 

  • Mascher, D.: Electrical and mechanical responses from ventricular muscle fibres after inactivation of the sodium carrying system. Pflügers Arch.317, 359–372 (1970)

    Article  PubMed  CAS  Google Scholar 

  • McElroy, W. T., Gerdes, A. J., Brown, E. B.: Effects of CO2, bicarbonate and pH on the performance of isolated perfused guinea pig hearts. Amer. J. Physiol.195, 412–416 (1958)

    PubMed  CAS  Google Scholar 

  • Morgenstern, M., Noack, E., Köhler, E.: The effects of isoprenaline and tyramine on the calcium uptake, the total calcium content and the contraction force of isolated guinea pig atria in dependence on different hydrogen ion concentrations. Naunyn-Schmiedeberg's Arch. Pharmacol.274, 125–137 (1972)

    Article  CAS  Google Scholar 

  • Nahas, G. G.: Effect of hydrocortisone on acidotic failure of the isolated heart. Circulat. Res.5, 489–492 (1957)

    PubMed  CAS  Google Scholar 

  • Nakamaru, Y., Schwartz, A.: Possible control of intracellular calcium metabolism by [H+]: sarcoplasmatic reticulum of skeletal and cardiac muscle. Biochem. biophys. Res. Commun.41, 830–836 (1970)

    Article  PubMed  CAS  Google Scholar 

  • Nawrath, H., McDonald, T.F., Trautwein, W.: The influence of cardiac glycosides on membrane currents in mammalian myocardium. Naunyn-Schmiedeberg's Arch. Pharmacol.287, R24 (1975)

    Google Scholar 

  • New, W., Trautwein, W.: Inward membrane currents in mammalian myocardium. Pflügers Arch334, 1–23 (1972)

    Article  PubMed  CAS  Google Scholar 

  • Poole-Wilson, P. A., Langer, G. A.: Effect of pH on ionic exchange and function in rat and rabbit myocardium. Amer. J. Physiol.229, 570–581 (1975)

    PubMed  CAS  Google Scholar 

  • Reuter, H.: Strom-Spannungsbeziehungen von Purkinje-Fasern bei verschiedenen extracellulären Calcium-Konzentrationen und unter Adrenalineinwirkung. Pflügers Arch. ges. Physiol.287, 357–367 (1966)

    Article  CAS  Google Scholar 

  • Reuter, H.: Divalent cations as charge carriers in excitable membranes. Progr. Biophys. molec. Biol.26, 3–43 (1973)

    Google Scholar 

  • Reuter, H., Beeler, G. W.: Calcium current and activation of contraction in ventricular myocardial fibres. Science163, 399–401 (1969)

    PubMed  CAS  Google Scholar 

  • Schädler, M.: Proportionale Aktivierung von ATPase-Aktivität und Kontraktionsspannung durch Calciumionen in isolierten contractilen Strukturen verschiedener Muskelarten. Pflügers Arch. ges. Physiol.296, 70–90 (1967)

    Article  Google Scholar 

  • Woodhull, A. M.: Ionic blockage of sodium channels in nerve. J. gen. Physiol.61, 687–708 (1973)

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Physiologisches Institut der Universität Freiburg, Hermann-Herder-Strasse 7, D-7800, Freiburg, Federal Republic of Germany

    M. Kohlhardt, K. Haap & H. R. Figulla

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  1. M. Kohlhardt
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  2. K. Haap
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  3. H. R. Figulla
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Kohlhardt, M., Haap, K. & Figulla, H.R. Influence of low extracellular pH upon the Ca inward current and isometric contractile force in mammalian ventricular myocardium. Pflugers Arch. 366, 31–38 (1976). https://doi.org/10.1007/BF02486557

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  • DOI: https://doi.org/10.1007/BF02486557

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