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. 1984 Feb 1;83(2):287–307. doi: 10.1085/jgp.83.2.287

The relationship among intracellular sodium activity, calcium, and strophanthidin inotropy in canine cardiac Purkinje fibers

PMCID: PMC2215632  PMID: 6325584

Abstract

The role of sodium and calcium ions in strophanthidin inotropy was studied by measuring simultaneously the electrical, mechanical, and intracellular sodium ion activities in electrically driven cardiac Purkinje fibers under conditions that change the intracellular sodium or calcium level (tetrodotoxin, strophanthidin, high calcium, and norepinephrine). Tetrodotoxin (TTX; 1-5 X 10(-6)M) shifted the action potential plateau to more negative values, shortened the action potential duration, and decreased the contractile tension and the intracellular sodium ion activity (aiNa). The changes in tension and in aiNa caused by TTX appear to be related since they had similar time courses. Strophanthidin (2-5 X 10(-7)M) increased tension and aiNa less in the presence of TTX, and, for any given value of aiNa, tension was less than in the absence of TTX. Increasing extracellular calcium (from 1.8 to 3.3-3.6 mM) or adding norepinephrine (0.5-1 X 10(-6)M) increased tension and decreased aiNa less in the presence than in the absence of TTX. When two of the above procedures were combined, the results were different. Thus, during the increase in aiNa and tension caused by strophanthidin in the presence of TTX, increasing calcium or adding norepinephrine increased tension markedly but did not increase aiNa further. In a TTX-high calcium or TTX-norepinephrine solution, adding strophanthidin increased both tension and aiNa, and the increase in tension was far greater than in the presence of TTX alone. The results indicate that: (a) the contractile force in Purkinje fibers is affected by a change in aiNa; (b) a decrease in aiNa by TTX markedly reduces the inotropic effect of strophanthidin, possibly as a consequence of depletion of intracellular calcium; (c) increasing calcium influx with norepinephrine or high calcium in the TTX-strophanthidin solution produces a potentiation of tension development, even if aiNa does not increase further; and (d) when the calcium influx is already increased by high calcium or norepinephrine, strophanthidin has its usual inotropic effect even in the presence of TTX. In conclusion, the positive inotropic effect of strophanthidin requires that an increase in aiNa be associated with suitable calcium availability.

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Selected References

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  1. Adams R. J., Schwartz A., Grupp G., Grupp I., Lee S. W., Wallick E. T., Powell T., Twist V. W., Gathiram P. High-affinity ouabain binding site and low-dose positive inotropic effect in rat myocardium. Nature. 1982 Mar 11;296(5853):167–169. doi: 10.1038/296167a0. [DOI] [PubMed] [Google Scholar]
  2. Allen D. G., Blinks J. R. Calcium transients in aequorin-injected frog cardiac muscle. Nature. 1978 Jun 15;273(5663):509–513. doi: 10.1038/273509a0. [DOI] [PubMed] [Google Scholar]
  3. Attwell D., Cohen I., Eisner D., Ohba M., Ojeda C. The steady state TTX-sensitive ("window") sodium current in cardiac Purkinje fibres. Pflugers Arch. 1979 Mar 16;379(2):137–142. doi: 10.1007/BF00586939. [DOI] [PubMed] [Google Scholar]
  4. Baker P. F., Blaustein M. P., Hodgkin A. L., Steinhardt R. A. The influence of calcium on sodium efflux in squid axons. J Physiol. 1969 Feb;200(2):431–458. doi: 10.1113/jphysiol.1969.sp008702. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bhattacharyya M. L., Vassalle M. Effects of tetrodotoxin on electrical and mechanical activity of cardiac Purkinje fibers. J Electrocardiol. 1982 Oct;15(4):351–360. doi: 10.1016/s0022-0736(82)81008-x. [DOI] [PubMed] [Google Scholar]
  6. Bhattacharyya M. L., Vassalle M. Role of calcium and sodium in strophanthidin inotropy in cardiac Purkinje fibers. Am J Physiol. 1981 Apr;240(4):H561–H570. doi: 10.1152/ajpheart.1981.240.4.H561. [DOI] [PubMed] [Google Scholar]
  7. Brody T. M., Akera T. Relations among Na+,K+-ATPase activity, sodium pump activity, transmembrane sodium movement, and cardiac contractility. Fed Proc. 1977 Aug;36(9):2219–2224. [PubMed] [Google Scholar]
  8. Carmeliet E., Vereecke J. Adrenaline and the plateau phase of the cardiac action potential. Importance of Ca++, Na+ and K+ conductance. Pflugers Arch. 1969;313(4):300–315. doi: 10.1007/BF00593955. [DOI] [PubMed] [Google Scholar]
  9. Caroni P., Carafoli E. An ATP-dependent Ca2+-pumping system in dog heart sarcolemma. Nature. 1980 Feb 21;283(5749):765–767. doi: 10.1038/283765a0. [DOI] [PubMed] [Google Scholar]
  10. Cohen C. J., Bean B. P., Colatsky T. J., Tsien R. W. Tetrodotoxin block of sodium channels in rabbit Purkinje fibers. Interactions between toxin binding and channel gating. J Gen Physiol. 1981 Oct;78(4):383–411. doi: 10.1085/jgp.78.4.383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Coraboeuf E., Deroubaix E., Coulombe A. Effect of tetrodotoxin on action potentials of the conducting system in the dog heart. Am J Physiol. 1979 Apr;236(4):H561–H567. doi: 10.1152/ajpheart.1979.236.4.H561. [DOI] [PubMed] [Google Scholar]
  12. Dagostino M., Lee C. O. Neutral carrier Na+- and Ca2+-selective microelectrodes for intracellular application. Biophys J. 1982 Dec;40(3):199–207. doi: 10.1016/S0006-3495(82)84475-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Deitmer J. W., Ellis D. The intracellular sodium activity of sheep heart Purkinje fibres: effects of local anaesthetics and tetrodotoxin. J Physiol. 1980 Mar;300:269–282. doi: 10.1113/jphysiol.1980.sp013161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fabiato A., Fabiato F. Calcium release from the sarcoplasmic reticulum. Circ Res. 1977 Feb;40(2):119–129. doi: 10.1161/01.res.40.2.119. [DOI] [PubMed] [Google Scholar]
  15. Gadsby D. C., Cranefield P. F. Two levels of resting potential in cardiac Purkinje fibers. J Gen Physiol. 1977 Dec;70(6):725–746. doi: 10.1085/jgp.70.6.725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gervais A., Lane L. K., Anner B. M., Lindenmayer G. E., Schwartz A. A possible molecular mechanism of the action of digitalis: ouabain action on calcium binding to sites associated with a purified sodium-potassium-activated adenosine triphosphatase from kidney. Circ Res. 1977 Jan;40(1):8–14. doi: 10.1161/01.res.40.1.8. [DOI] [PubMed] [Google Scholar]
  17. Glitsch H. G., Reuter H., Scholz H. The effect of the internal sodium concentration on calcium fluxes in isolated guinea-pig auricles. J Physiol. 1970 Jul;209(1):25–43. doi: 10.1113/jphysiol.1970.sp009153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hougen T. J., Spicer N., Smith T. W. Stimulation of monovalent cation active transport by low concentrations of cardiac glycosides. Role of catecholamines. J Clin Invest. 1981 Nov;68(5):1207–1214. doi: 10.1172/JCI110366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kao C. Y. Tetrodotoxin, saxitoxin and their significance in the study of excitation phenomena. Pharmacol Rev. 1966 Jun;18(2):997–1049. [PubMed] [Google Scholar]
  20. Lee C. O., Dagostino M. Effect of strophanthidin on intracellular Na ion activity and twitch tension of constantly driven canine cardiac Purkinje fibers. Biophys J. 1982 Dec;40(3):185–198. doi: 10.1016/S0006-3495(82)84474-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lee C. O., Kang D. H., Sokol J. H., Lee K. S. Relation between intracellular Na ion activity and tension of sheep cardiac Purkinje fibers exposed to dihydro-ouabain. Biophys J. 1980 Feb;29(2):315–330. doi: 10.1016/S0006-3495(80)85135-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lee C. O., Vassalle M. Modulation of intracellular Na+ activity and cardiac force by norepinephrine and Ca2+. Am J Physiol. 1983 Jan;244(1):C110–C114. doi: 10.1152/ajpcell.1983.244.1.C110. [DOI] [PubMed] [Google Scholar]
  23. Lee K. S., Klaus W. The subcellular basis for the mechanism of inotropic action of cardiac glycosides. Pharmacol Rev. 1971 Sep;23(3):193–261. [PubMed] [Google Scholar]
  24. Lin C. I., Vassalle M. Role of sodium in strophanthidin toxicity of Purkinje fibers. Am J Physiol. 1978 Apr;234(4):H477–H486. doi: 10.1152/ajpheart.1978.234.4.H477. [DOI] [PubMed] [Google Scholar]
  25. Marban E., Tsien R. W. Enhancement of calcium current during digitalis inotropy in mammalian heart: positive feed-back regulation by intracellular calcium? J Physiol. 1982 Aug;329:589–614. doi: 10.1113/jphysiol.1982.sp014321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Noble D. Mechanism of action of therapeutic levels of cardiac glycosides. Cardiovasc Res. 1980 Sep;14(9):495–514. doi: 10.1093/cvr/14.9.495. [DOI] [PubMed] [Google Scholar]
  27. Pappano A. J. Calcium-dependent action potentials produced by catecholamines in guinea pig atrial muscle fibers depolarized by potassium. Circ Res. 1970 Sep;27(3):379–390. doi: 10.1161/01.res.27.3.379. [DOI] [PubMed] [Google Scholar]
  28. Reuter H. Properties of two inward membrane currents in the heart. Annu Rev Physiol. 1979;41:413–424. doi: 10.1146/annurev.ph.41.030179.002213. [DOI] [PubMed] [Google Scholar]
  29. Reuter H., Scholz H. The regulation of the calcium conductance of cardiac muscle by adrenaline. J Physiol. 1977 Jan;264(1):49–62. doi: 10.1113/jphysiol.1977.sp011657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Reuter H., Seitz N. The dependence of calcium efflux from cardiac muscle on temperature and external ion composition. J Physiol. 1968 Mar;195(2):451–470. doi: 10.1113/jphysiol.1968.sp008467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Reuter H. The dependence of slow inward current in Purkinje fibres on the extracellular calcium-concentration. J Physiol. 1967 Sep;192(2):479–492. doi: 10.1113/jphysiol.1967.sp008310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Rougier O., Vassort G., Garnier D., Gargouil Y. M., Coraboeuf E. Existence and role of a slow inward current during the frog atrial action potential. Pflugers Arch. 1969;308(2):91–110. doi: 10.1007/BF00587018. [DOI] [PubMed] [Google Scholar]
  33. Sheu S. S., Fozzard H. A. Transmembrane Na+ and Ca2+ electrochemical gradients in cardiac muscle and their relationship to force development. J Gen Physiol. 1982 Sep;80(3):325–351. doi: 10.1085/jgp.80.3.325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Vassalle M., Bhattacharyya M. Interactions of norepinephrine and strophanthidin in cardiac Purkinje fibers. Int J Cardiol. 1981;1(2):179–194. doi: 10.1016/0167-5273(81)90031-0. [DOI] [PubMed] [Google Scholar]
  35. Vassalle M., Lin C. I. Effect of calcium on strophanthidin-induced electrical and mechanical toxicity in cardiac Purkinje fibers. Am J Physiol. 1979 May;236(5):H689–H697. doi: 10.1152/ajpheart.1979.236.5.H689. [DOI] [PubMed] [Google Scholar]
  36. Wasserstrom J. A., Schwartz D. J., Fozzard H. A. Catecholamine effects on intracellular sodium activity and tension in dog heart. Am J Physiol. 1982 Nov;243(5):H670–H675. doi: 10.1152/ajpheart.1982.243.5.H670. [DOI] [PubMed] [Google Scholar]
  37. Wier W. G. Calcium transients during excitation-contraction coupling in mammalian heart: aequorin signals of canine Purkinje fibers. Science. 1980 Mar 7;207(4435):1085–1087. doi: 10.1126/science.7355274. [DOI] [PubMed] [Google Scholar]

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