A quantitative relationship between cellular Na accumulation and relaxation produced by ouabain in the depolarized smooth muscle of guinea-pig taenia coli

  • Tadashi Kishimoto
  • Hiroshi Ozaki
  • Norimoto Urakawa
Article

Summary

  1. 1.

    An investigation was made of the effect of oubain on the membrane potential, tension development,45Ca uptake and intracellular Na and K contents of smooth muscle of the guinea-pig taenia coli depolarized by high-K solution. The results were compared with the effects of 2,4-dinitrophenol (DNP) and verapamil.

     
  2. 2.

    All drugs produced concentration-dependent relaxations of high-K induced contractures without affecting the depolarization of the membrane. After removal of Na from the medium, the contracture was inhibited by DNP or verapamil but not by ouabain. The inhibitory effects of ouabain and verapamil were antagonized by raising the concentration of external Ca ([Ca]0), but the relaxation produced by DNP was independent of [Ca]0.

     
  3. 3.

    Estimates of cellular Na were made by bathing the tissues in cold Li-solution. After an initial rapid loss of Na due to an exchange of extracellular Na with Li, the tissue Na reached a steady state. The residual after 1 h was regarded as cellular Na.

     
  4. 4.

    During relaxation induced by ouabain, the depolarized muscle gained cellular Na. The increase in cellular Na was dependent upon the concentration of ouabain. A smaller increase was noted with DNP, while verapamil had no effect on cellular Na.

     
  5. 5.

    The relaxation produced by ouabain was related to the intracellular Na content of the tissues. Also, the magnitude of the contraction produced by adding 1 mM Ca to Ca-free K-depolarized tissues was inversely correlated with the logarithm of the intracellular Na content, and an increase in the Na from 7.3–26.6 mmole/kg wet wt. halved the size of the Ca contracture.

     
  6. 6.

    45Ca uptake, which was measured by a modified “La-method”, was increased in high-K solution. This increase was inhibited by pretreatments with ouabain, DNP and verapamil.

     
  7. 7.

    It is suggested that the action of ouabain is closely related to an accumulation of cellular Na, which may cause the relaxation mainly by inhibiting Ca influx in response to depolarization with high-K. The data also suggest that the mechanism of relaxation induced by DNP or verapamil is different from that induced by ouabain.

     

Key words

Ouabain Taenia coli Cellular Na Relaxation Depolarization 

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References

  1. Axelsson, J., Holmberg, B.: The effects of K+-free solution on tension development in the smooth muscle taenia coli from the guinea pig. Acta Physiol. Scand.82, 322–332 (1971)Google Scholar
  2. Bose, D.: Mechanism of mechanical inhibition of smooth muscle by ouabain. Br. Pharmacol.55, 111–116 (1975)Google Scholar
  3. Brading, A. F.: Calcium-induced increase in membrane permeability in the guinea-pig taenia coli: evidence for involvement of a sodium-calcium exchange mechanism. J. Physiol.275, 65–84 (1978)Google Scholar
  4. Bülbring, E., Burnstock, G.: Membrane potential changes associated with tachyphylaxis and potentiation of the response to stimulating drugs in smooth muscle. Br. J. Pharmacol. Chemother.15, 611–624 (1960)Google Scholar
  5. Casteels, R., van Breemen, C.: Active and passive Ca fluxes across cell membranes of the guinea-pig taenia coli. Pflügers Arch.359, 197–207 (1975)Google Scholar
  6. Crankshaw, D. J., Janis, R. A., Daniel, E. E.: The effects of Ca2+ antagonists on Ca2+ accumulations by subcellular fractions of rat myometrium. Can. J. Physiol. Pharmacol.55, 1028–1032 (1977)Google Scholar
  7. Friedman, S. M.: Lithium substitution and the distribution of sodium in the rat tail artery. Circ. Res.34, 168–175 (1974)Google Scholar
  8. Friedman, S. M.: Sodium in blood vessels. Blood Vessels16, 2–16 (1979)Google Scholar
  9. Friedman, S. M., Mar, M., Nakashima, M. Lithium substitution analysis of Na and K phases in a small artery. Blood Vessels,11, 55–64 (1974)Google Scholar
  10. Ganeshanandan, S. S., Karaki, H., Ikeda, M., Urakawa, N.: Mechanical response of guinea pig taenia coli in high-K/Na-deficient medium under anoxia. Jpn. J. Pharmacol.19, 329–330 (1969)Google Scholar
  11. Karaki, H., Ganeshanandan, S. S., Ikeda, M., Urakawa, N.: Changes in tension, Ca movement and metabolism of guinea pig taenia coli in varying concentrations of external Na and K. Jpn. J. Pharmacol.19, 569–577 (1969)Google Scholar
  12. Karaki, H., Ikeda, M., Urakawa, N.: Effects of ouabain and 2,4-dinitrophenol on calcium distribution and exchange in guinea pig taenia coli in high-potassium solution. Jpn. J. Pharmacol.20, 530–535 (1970)Google Scholar
  13. Karaki, H., Weiss, G. B.: Alteration in high and low affinity binding of45Ca in rabbit aorta by norepinephrine and potassium after exposure to lanthanum and low temperature. J. Pharmacol. Exp. Ther.211, 86–92 (1979)Google Scholar
  14. Katase, T., Tomita, T.: Influences of sodium and calcium on the recovery process from potassium contracture in the guinea-pig taenia coli. J. Physiol.224, 489–500 (1972)Google Scholar
  15. Mayer, C. J., van Breemen, C., Casteels,R.: The action of lanthanum and D 600 on the calcium exchange in the smooth muscle cells of the guinea-pig taenia coli Pflügers Arch.337 333–350 (1972)Google Scholar
  16. Pfaffman, M., Holland, W. C.: Effects of ouabain and 2,4-dinitrophenol on Ca exchange in taenia coli. Am. J. Physiol.211, 400–402 (1966)Google Scholar
  17. Pfaffman, M., Urakawa, N., Holland, W. C.: Role of metabolism in K-induced tension changes in guinea pig taenia coli. Am. J. Physiol.208, 1203–1205 (1965)Google Scholar
  18. Riemer, J., Dörfler, F., Mayer, C. J., Ulbrecht, G.: Calcium-antagonistic effects on the spontaneous activity of guinea-pig taenia coli. Pflügers Arch.351, 241–258 (1974)Google Scholar
  19. Schatzmann, H. J., Ackermann, H.: Die Strophanthinwirkung am Darmmuskel und ihre Beziehung zum Kationengehalt des Mediums. Helv. Physiol. Acta19, 196–213 (1961)Google Scholar
  20. Simmons, N. L., Naftalin, R. J.: Factors affecting the compartmentalization of sodium ion within rabbit ileum in vitro. Biochim. Biophys. Acta448, 411–425 (1976)Google Scholar
  21. Urakawa, N., Karaki, H., Ikeda, M.: Effects of ouabain and metabolic inhibiting factors on Ca distribution during K-induced contracture in guinea pig taenia coli. Jpn. J. Pharmacol.20, 360–366 (1970)Google Scholar
  22. Urakawa, N., Ziegler, A.: The relationship between the Na and K content of guinea-pig taenia coli and its response to ouabain. Naunyn-Schmiedeberg's Arch. Pharmacol.293, 172 (1976)Google Scholar
  23. van Breemen, C., Farinas, R., Casteels, R., Gerba, P., Wuytack, F., Deth, R.: Factors controlling cytoplasmic Ca2+ concentration. Phil. Trans. R. Soc. (Lond.) B265, 57–71 (1973)Google Scholar
  24. van Breemen, C., Wuytack, F., Casteels, R.:Stimulation of45Ca efflux from smooth muscle cells by metabolic inhibition and high K depolarization. Pflügers Arch.359, 183–196 (1975)Google Scholar
  25. Weiss, G. B., Karaki, H., Hester, R. K.: Specificity of nitroprusside for inhibition of release of high affinity calcium ion in canine renal arteries. Fed. Proc.38, 367 (1979)Google Scholar

Copyright information

© Springer-Verlag 1980

Authors and Affiliations

  • Tadashi Kishimoto
    • 1
  • Hiroshi Ozaki
    • 1
  • Norimoto Urakawa
    • 1
  1. 1.Department of Veterinary Pharmacology, Faculty of AgricultureUniversity of TokyoTokyoJapan

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