The Effects of Intracellular Na on Contraction and Intracellular pH in Mammalian Cardiac Muscle

  • R. D. Vaughan-Jones
  • D. A. Eisner
  • W. J. Lederer
Part of the Advances in Myocardiology book series (ADMY)

Abstract

Intracelluar Na and pH were measured with recessed-tip ion-selective microelectrodes in voltage-clamped sheep cardiac Purkinje fibers. Intracellular Na activity a Na i was elevated by inhibiting the Na/K pump. This produced an increase of twitch tension that had a steep dependence on the increase of a Na i . These effects of a Na i on twitch tension are probably mediated by an Na-Ca exchange. An increase of a Na i also produced a component of tonic tension that appears to be produced directly by the Na-Ca exchange. The dependence of tonic tension and a Na i on membrane potential suggests that this exchange process may be voltage-sensitive. The increase of a Na i is associated with an intracellular acidification that appears to be secondary to an increase of [Ca2+]i produced by Na-Ca exchange. Therefore, as well as affecting [Ca2+]i, Na-Ca exchange can under some circumstances influence pHi indirectly, and this complicates the interpretation of changes in tension,. since protons and Ca ions have opposite effects on contractile force.

Keywords

Membrane Potential Myocardial Contraction Tonic Contracture Squid Axon Cardiac Purkinje Fibre 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Ringer, S. 1883. A further contribution regarding the influence of the different constituents of the blood on the contraction of the heart. J. Physiol. 4:29–42.PubMedGoogle Scholar
  2. 2.
    Baker, P. F., Blaustein, M. P., Hodgkin, A. L., and Steinhardt, R. A. 1969. The influence of calcium on sodium efflux in squid axons. J. Physiol. 200:431–458.PubMedGoogle Scholar
  3. 3.
    Glitsch, H. G., Reuter, H., and Scholz, H. 1970. The effect of the internal sodium concentration on calcium fluxes in isolated guinea-pig auricles. J. Physiol. 204:25–43.Google Scholar
  4. 4.
    Ellis, D. 1977. The effects of external cations and ouabain on the intracellular sodium activity of sheep heart Purkinje fibres. J. Physiol. 273:211–240.PubMedGoogle Scholar
  5. 5.
    Lee, C. O., Kang, D. H., Sokol, J. H., and Lee, K. S. 1980. Relation between intracellular Na ion activity and tension of sheep cardiac Purkinje fibers exposed to dihydro-ouabain. Biophys. J. 29:315–330.PubMedCrossRefGoogle Scholar
  6. 6.
    Cohen, C. J., Fozzard, H. A., and Sheu, S.-S. 1982. Increase in intracellular sodium ion activity during stimulation in mammalian cardiac muscle. Circ. Res. 50:651–662.PubMedCrossRefGoogle Scholar
  7. 7.
    Eisner, D. A., Lederer, W. J., and Vaughan-Jones, R. D. 1981. The dependence of sodium pumping and tension on intracellular sodium activity in voltage-clamped sheep cardiac Purkinje fibres. J. Physiol. 317:163–187.PubMedGoogle Scholar
  8. 8.
    Lederer, W. J., and Sheu, S.-S . 1983. Heart-rate dependent changes in intracellular sodium activity and twitch tension in sheep cardiac Purkinje fibres. J. Physiol. 345:44P.Google Scholar
  9. 9.
    Noble, D. 1980. Mechanism of action of therapeutic levels of cardiac glycosides. Cardiovasc. Res. 14:495–514.PubMedCrossRefGoogle Scholar
  10. 10.
    Gaskell, W. H. 1880. On the tonicity of the heart and blood vessels. J. Physiol. 3:48–75.PubMedGoogle Scholar
  11. 11.
    Allen, D. G., and Orchard, C. H. 1983. The effect of changes of pH on intracellular calcium transients in mammalian cardiac muscle. J. Physiol. 335:555–567.PubMedGoogle Scholar
  12. 12.
    Thomas, R. C. 1978. Ion-sensitive Micro-electrodes. Academic Press, New York and London.Google Scholar
  13. 13.
    Karagueuzian, H. S., and Katzung, B. G. 1982. Voltage-clamp studies of transient inward current and mechanical oscillations induced by ouabain in ferret papillary muscle. J. Physiol. 327:255–271.PubMedGoogle Scholar
  14. 14.
    Eisner, D. A., and Lederer, W. J. 1980. Characterization of the electrogenic sodium pump in cardiac Purkinje fibres. J. Physiol. 303:441–474.PubMedGoogle Scholar
  15. 15.
    Gadsby, D. C., and Cranefield, P. F. 1979. Direct measurement of changes in sodium pump current in canine cardiac Purkinje fibres. Proc. Natl. Acad. Sci. U.S.A. 76:1783–1787.PubMedCrossRefGoogle Scholar
  16. 16.
    Eisner, D. A., Lederer, W. J., and Vaughan-Jones, R. D. 1983. The relationship between twitch tension and intracellular Na activity in sheep cardiac Purkinje fibres. J. Physiol. 341:28–29P.Google Scholar
  17. 17.
    Marban, E., and Tsien, R. W. 1982. Enhancement of cardiac calcium current during digitalis inotropy: Positive feedback regulation by intracellular calcium? J. Physiol. 329:589–614.PubMedGoogle Scholar
  18. 18.
    Lederer, W. J., and Eisner, D. A. 1982. The effects of sodium pump activity on the slow inward current in sheep cardiac Purkinje fibres. Proc. R. Soc. Lond. 214:249–262.PubMedCrossRefGoogle Scholar
  19. 19.
    Mullins, L. J., and Requena, J. 1981. The “late” Ca channel in squid axons. J. Gen. Physiol. 78:683–700.PubMedCrossRefGoogle Scholar
  20. 20.
    Horackova, M., and Vassort, G. 1979. Sodium-calcium exchange in regulation of cardiac contractility: Evidence for an electrogenic, voltage-dependent mechanism. J. Gen. Phsyiol. 73:403–424.CrossRefGoogle Scholar
  21. 21.
    Chapman, R. A., and Tunstall, J. 1980. The interaction of sodium and calcium ions at the cell membrane and the control of contractile strength in frog atrial muscle. J. Physiol. 305 :109–123 .PubMedGoogle Scholar
  22. 22.
    Eisner, D. A., Lederer, W. J., and Vaughan-Jones, R. D. 1983. The control of tonic tension by membrane potential and intracellular Na activity in the sheep cardiac Purkinje fibre. J. Physiol. 335 : 723–743 .PubMedGoogle Scholar
  23. 23.
    Eisner, D. A., and Lederer, W. J. 1979. Inotropic and arrhythmogenic effects of potassium depleted solutions on mammalian cardiac muscle. J. Physiol. 294:255–277.PubMedGoogle Scholar
  24. 24.
    Eisner, D. A., and Lederer, W. J. 1982. Effects of caffeine on the transient inward current in cardiac Purkinje fibres. J. Physiol. 322:48–49P.Google Scholar
  25. 25.
    Leoty, C., and Raymond, G. 1972. Mechanical activity and ionic currents in frog atrial trabeculae. Pfluegers Arch. 334:114–128.CrossRefGoogle Scholar
  26. 26.
    Blaustein, M. P., and Hodgkin, A. L. 1969. The effect of cyanide on the efflux of calcium from squid axons. J. Physiol. 200:497–528.PubMedGoogle Scholar
  27. 27.
    Sheu, S-S., and Fozzard, H. A. 1982. Transmembrane Na+ and Ca2+ electrochemical gradients in cardiac muscle and their relationship to force development. J. Gen. Physiol. 80:325–351.PubMedCrossRefGoogle Scholar
  28. 28.
    Pitts, B. J. R. 1979. Stoichiometry of sodium-calcium exchange in cardiac sarcolemmal vesicles. J. Biol. Chem. 254:6232–6235.PubMedGoogle Scholar
  29. 29.
    Reeves, J. P., and Sutko, J. L. 1979. Sodium-calcium ion exchange in cardiac sarcolemmal vesicles. Proc. Natl. Acad. Sci. U.S.A. 76:590–594.PubMedCrossRefGoogle Scholar
  30. 30.
    Philipson, K. D., and Nishimoto, A. Y. 1980. Na+-Ca2+ exchange is affected by membrane potential in cardiac sarcolemmal vesicles. J. Biol. Chem. 255:6880–6882.PubMedGoogle Scholar
  31. 31.
    Orchard, C. H., Eisner, D. A., and Allen, D. G. 1983. Oscillations of intracellular Ca2+ in mammalian cardiac muscle. Nature 304:735–738.PubMedCrossRefGoogle Scholar
  32. 32.
    Wier, W. G., Kort, A. A., Stern, M. D., Lakatta, E. G., and Marban E. 1983. Cellular calcium fluctuations in mammalian heart: Direct evidence from noise analysis of aequorin signals in Purkinje fibers. Proc. Natl. Acad. Sci. U.S.A. 80:7361–7371.CrossRefGoogle Scholar
  33. 33.
    Deitmer, J. W., and Ellis, D. 1980. Interactions between the regulation of the intracellular pH and sodium activity of sheep cardiac Purkinje fibres. J. Physiol. 304:471–488.PubMedGoogle Scholar
  34. 34.
    Meech, R. W., and Thomas, R. C. 1980. Effect of measured calcium chloride injections on the membrane potential and internal pH of snail neurones. J. Physiol. 298:111–129.PubMedGoogle Scholar
  35. 35.
    Deitmer, J. W., and Ellis, D. 1978. Changes in the intracellular sodium activity of sheep heart Purkinje fibres produced by calcium and other divalent cations. J. Physiol. 277:437–453.PubMedGoogle Scholar
  36. 36.
    Eisner, D. A., Orchard, C. H., and Allen, D. G. 1984. Control of intracellular ionized calcium concentration by sarcolemmal and intracellular mechanisms. J. Mol. Cell. Cardiol. 16:137–146.PubMedCrossRefGoogle Scholar
  37. 37.
    Bers, D. M., and Ellis, D. 1982. Intracellular calcium and sodium activity in sheep heart Purkinje fibres: Effects of changes of external sodium and intracellular pH. Pfluegers Arch. 393:171–178.CrossRefGoogle Scholar
  38. 38.
    Vaughan-Jones, R. D., Lederer, W. J., and Eisner, D. A. 1983. Ca2+ ions can affect intracellular pH in mammalian cardiac muscle. Nature 301:522–524.PubMedCrossRefGoogle Scholar
  39. 39.
    Poole-Wilson, P. A. 1978. Measurement of myocardial intracellular pH in pathological states. J. Mol. Cell. Cardiol. 10:511–526.PubMedCrossRefGoogle Scholar
  40. 40.
    Fabiato, A., and Fabiato, F. 1978. Effects of pH on the myofilaments and the sarcoplasmic reticulum of skinned cells from cardiac and skeletal muscles. J. Physiol. 276:233–255.PubMedGoogle Scholar
  41. 41.
    Eisner, D. A., Lederer, W. J., and Vaughan-Jones, R. D. 1983. The relationship between intracellular pH and contraction in sheep cardiac Purkinje fibres. J. Physiol. 334:106–107P.Google Scholar

Copyright information

© Springer Science+Business Media New York 1985

Authors and Affiliations

  • R. D. Vaughan-Jones
    • 1
  • D. A. Eisner
    • 2
  • W. J. Lederer
    • 3
  1. 1.University Laboratory of PhysiologyOxfordEngland
  2. 2.Department of PhysiologyUniversity College LondonLondonEngland
  3. 3.Department of PhysiologyUniversity of Maryland Medical SchoolBaltimoreUSA

Personalised recommendations