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. 1984 Mar 1;83(3):417–433. doi: 10.1085/jgp.83.3.417

Excitation-contraction coupling in cardiac Purkinje fibers. Effects of caffeine on the intracellular [Ca2+] transient, membrane currents, and contraction

PMCID: PMC2215642  PMID: 6325589

Abstract

The effects of caffeine on tension, membrane potential, membrane currents, and intracellular [Ca2+], measured as the light emitted by the Ca2+-activated photoprotein aequorin, were studied in canine cardiac Purkinje fibers. An initial, transient, positive inotropic effect of caffeine was accompanied by a transient increase in the second component of the aequorin signal (L2) but not the first (L1). In the steady state, 4 or 10 mM caffeine always decreased twitch tension and greatly reduced both L1 and L2. At a concentration of 2 mM, caffeine usually reduced but occasionally increased the steady state twitch tension. However, 2 mM caffeine always reduced both L1 and L2. Caffeine eliminated the diastolic oscillations of intracellular [Ca2+] induced by high extracellular [Ca2+]. In voltage-clamp experiments, 10 mM caffeine reduced the transient outward current and the peak tension elicited by step depolarization from a holding potential of -45 mV. In the presence of 20 mM Cs+, 10 mM caffeine reduced slow inward current. However, the time course of this reduction was far slower than that in tension and light observed in separate experiments. The simplest explanation of the results is that caffeine inhibits the sequestration of Ca2+ by the sarcoplasmic reticulum. The results also suggest that in Purkinje fibers caffeine increases the sensitivity of the myofilaments to Ca2+.

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Selected References

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  1. 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]
  2. Allen D. G., Kurihara S. Calcium transients in mammalian ventricular muscle. Eur Heart J. 1980;Suppl A:5–15. doi: 10.1093/eurheartj/1.suppl_1.5. [DOI] [PubMed] [Google Scholar]
  3. Blinks J. R., Olson C. B., Jewell B. R., Bravený P. Influence of caffeine and other methylxanthines on mechanical properties of isolated mammalian heart muscle. Evidence for a dual mechanism of action. Circ Res. 1972 Apr;30(4):367–392. doi: 10.1161/01.res.30.4.367. [DOI] [PubMed] [Google Scholar]
  4. Cameliet E. Decrease of K efflux and influx by external Cs ions in cardiac Purkinje and muscle cells. Pflugers Arch. 1980 Jan;383(2):143–150. doi: 10.1007/BF00581875. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Chapman R. A., Léoty C. The time-dependent and dose-dependent effects of caffeine on the contraction of the ferret heart. J Physiol. 1976 Apr;256(2):287–314. doi: 10.1113/jphysiol.1976.sp011326. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Clark A., Olson C. B. Effects of caffeine and isoprenaline on mammalian ventricular muscle. Br J Pharmacol. 1973 Jan;47(1):1–11. doi: 10.1111/j.1476-5381.1973.tb08153.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Colatsky T. J., Tsien R. W. Electrical properties associated with wide intercellular clefts in rabbit Purkinje fibres. J Physiol. 1979 May;290(2):227–252. doi: 10.1113/jphysiol.1979.sp012769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Coraboeuf E., Carmeliet E. Existence of two transient outward currents in sheep cardiac Purkinje fibers. Pflugers Arch. 1982 Feb;392(4):352–359. doi: 10.1007/BF00581631. [DOI] [PubMed] [Google Scholar]
  10. DECK K. A., KERN R., TRAUTWEIN W. VOLTAGE CLAMP TECHNIQUE IN MAMMALIAN CARDIAC FIBRES. Pflugers Arch Gesamte Physiol Menschen Tiere. 1964 Jun 9;280:50–62. doi: 10.1007/BF00412615. [DOI] [PubMed] [Google Scholar]
  11. DEGUBAREFF T., SLEATOR W., Jr EFFECTS OF CAFFEINE ON MAMMALIAN ATRIAL MUSCLE, AND ITS INTERACTION WITH ADENOSINE AND CALCIUM. J Pharmacol Exp Ther. 1965 May;148:202–214. [PubMed] [Google Scholar]
  12. Eisner D. A., Lederer W. J. Characterization of the electrogenic sodium pump in cardiac Purkinje fibres. J Physiol. 1980 Jun;303:441–474. doi: 10.1113/jphysiol.1980.sp013298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Endo M. Calcium release from the sarcoplasmic reticulum. Physiol Rev. 1977 Jan;57(1):71–108. doi: 10.1152/physrev.1977.57.1.71. [DOI] [PubMed] [Google Scholar]
  14. Fabiato A., Fabiato F. Activation of skinned cardiac cells. Subcellular effects of cardioactive drugs. Eur J Cardiol. 1973 Dec;1(2):143–155. [PubMed] [Google Scholar]
  15. Fabiato A., Fabiato F. Calcium-induced release of calcium from the sarcoplasmic reticulum of skinned cells from adult human, dog, cat, rabbit, rat, and frog hearts and from fetal and new-born rat ventricles. Ann N Y Acad Sci. 1978 Apr 28;307:491–522. doi: 10.1111/j.1749-6632.1978.tb41979.x. [DOI] [PubMed] [Google Scholar]
  16. Fabiato A., Fabiato F. Excitation-contraction coupling of isolated cardiac fibers with disrupted or closed sarcolemmas. Calcium-dependent cyclic and tonic contractions. Circ Res. 1972 Sep;31(3):293–307. doi: 10.1161/01.res.31.3.293. [DOI] [PubMed] [Google Scholar]
  17. Fabiato A., Fabiato F. Techniques of skinned cardiac cells and of isolated cardiac fibers with disrupted sarcolemmas with reference to the effects of catecholamines and of caffeine. Recent Adv Stud Cardiac Struct Metab. 1976;9:1–94. [PubMed] [Google Scholar]
  18. Fozzard H. A., Hiraoka M. The positive dynamic current and its inactivation properties in cardiac Purkinje fibres. J Physiol. 1973 Nov;234(3):569–586. doi: 10.1113/jphysiol.1973.sp010361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Goto M., Yatani A., Ehara T. Interaction between caffeine and adenosine on the membrane current and tension component in the bullfrog atrial muscle. Jpn J Physiol. 1979;29(4):393–409. doi: 10.2170/jjphysiol.29.393. [DOI] [PubMed] [Google Scholar]
  20. Guerin M., Wallon G. The reversible replacement of internal potassium by caesium in isolated turtle heart. J Physiol. 1979 Aug;293:525–537. doi: 10.1113/jphysiol.1979.sp012905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Henderson A. H., Brutsaert D. L., Forman R., Sonnenblick E. H. Influence of caffeine on force development and force-frequency relations in cat and rat heart muscle. Cardiovasc Res. 1974 Mar;8(2):162–172. doi: 10.1093/cvr/8.2.162. [DOI] [PubMed] [Google Scholar]
  22. Kass R. S., Lederer W. J., Tsien R. W., Weingart R. Role of calcium ions in transient inward currents and aftercontractions induced by strophanthidin in cardiac Purkinje fibres. J Physiol. 1978 Aug;281:187–208. doi: 10.1113/jphysiol.1978.sp012416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kass R. S., Siegelbaum S. A., Tsien R. W. Three-micro-electrode voltage clamp experiments in calf cardiac Purkinje fibres: is slow inward current adequately measured? J Physiol. 1979 May;290(2):201–225. doi: 10.1113/jphysiol.1979.sp012768. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kenyon J. L., Gibbons W. R. Influence of chloride, potassium, and tetraethylammonium on the early outward current of sheep cardiac Purkinje fibers. J Gen Physiol. 1979 Feb;73(2):117–138. doi: 10.1085/jgp.73.2.117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kimoto Y. Effects of caffeine on the membrane potentials and contractility of the guinea pig atrium. Jpn J Physiol. 1972 Apr;22(2):225–238. doi: 10.2170/jjphysiol.22.225. [DOI] [PubMed] [Google Scholar]
  26. Marban E. Inhibition of transient outward current by intracellular ion substitution unmasks slow inward calcium current in cardiac Purkinje fibers. Pflugers Arch. 1981 Apr;390(1):102–106. doi: 10.1007/BF00582721. [DOI] [PubMed] [Google Scholar]
  27. Morgan J. P., Blinks J. R. Intracellular Ca2+ transients in the cat papillary muscle. Can J Physiol Pharmacol. 1982 Apr;60(4):524–528. doi: 10.1139/y82-072. [DOI] [PubMed] [Google Scholar]
  28. NAYLER W. G. Effect of caffeine on cardiac contractile activity and radiocalcium movement. Am J Physiol. 1963 Jun;204:969–974. doi: 10.1152/ajplegacy.1963.204.6.969. [DOI] [PubMed] [Google Scholar]
  29. Niedergerke R., Page S. Analysis of caffeine action in single trabeculae of the frog heart. Proc R Soc Lond B Biol Sci. 1981 Nov 13;213(1192):303–324. doi: 10.1098/rspb.1981.0068. [DOI] [PubMed] [Google Scholar]
  30. Oba M. Effects of caffeine on tension development in dog papillary muscle under voltage clamp. Jpn J Physiol. 1973 Feb;23(1):47–58. [PubMed] [Google Scholar]
  31. Siegelbaum S. A., Tsien R. W. Calcium-activated transient outward current in calf cardiac Purkinje fibres. J Physiol. 1980 Feb;299:485–506. doi: 10.1113/jphysiol.1980.sp013138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Siegelbaum S. A., Tsien R. W., Kass R. S. Role of intracellular calcium in the transient outward current of calf Purkinje fibres. Nature. 1977 Oct 13;269(5629):611–613. doi: 10.1038/269611a0. [DOI] [PubMed] [Google Scholar]
  33. Tillotson D., Horn R. Inactivation without facilitation of calcium conductance in caesium-loaded neurones of Aplysia. Nature. 1978 May 25;273(5660):312–314. doi: 10.1038/273312a0. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. 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]
  36. Wier W. G., Hess P. Excitation-contraction coupling in cardiac Purkinje fibers. Effects of cardiotonic steroids on the intracellular [Ca2+] transient, membrane potential, and contraction. J Gen Physiol. 1984 Mar;83(3):395–415. doi: 10.1085/jgp.83.3.395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Wier W. G., Isenberg G. Intracellular [Ca2+] transients in voltage clamped cardiac Purkinje fibers. Pflugers Arch. 1982 Jan;392(3):284–290. doi: 10.1007/BF00584312. [DOI] [PubMed] [Google Scholar]

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