Skip to main content
NCBI home page
The Journal of General Physiology logoLink to The Journal of General Physiology
. 1988 Sep 1;92(3):351–368. doi: 10.1085/jgp.92.3.351

Effects of rapid application of caffeine on intracellular calcium concentration in ferret papillary muscles

PMCID: PMC2228902  PMID: 3225553

Abstract

In this paper we investigate the effects of caffeine (5-20 mM) on ferret papillary muscle. The intracellular Ca2+ concentration ( [Ca2+]i) was measured from the light emitted by the photoprotein aequorin, which had previously been microinjected into superficial cells. Isometric tension was measured simultaneously. The rapid application of caffeine produced a transient increase of [Ca2+]i, which decayed spontaneously within 2-3 s and was accompanied by a transient contracture. The removal of extracellular Na+ or an increase in the concentration of intracellular Na+ (produced by strophanthidin) increased the magnitude of the caffeine response. Cessation of stimulation for several minutes or stimulation at low rates decreased the magnitude of the stimulated twitch and Ca2+ transient. These maneuvers also decreased the size of the caffeine response. These results are consistent with the hypothesis that the caffeine-releasable pool of Ca2+ (sarcoplasmic reticulum) is modulated by maneuvers that affect contraction. Ryanodine (10 microM) decreased the magnitude of the caffeine response as well as that of the stimulated twitch. In contrast, the rapid removal of external Ca2+ abolished the systolic Ca2+ transient within 5 s, but had no effect on the caffeine response. From this we conclude that the abolition of twitch by Ca2+-free solutions is not due to depletion of the sarcoplasmic reticulum of Ca2+, but may be due to a requirement of Ca2+ entry into the cell to trigger Ca2+ release from the sarcoplasmic reticulum.

Full Text

The Full Text of this article is available as a PDF (900.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  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., Blinks J. R., Prendergast F. G. Aequorin luminescence: relation of light emission to calcium concentration--a calcium-independent component. Science. 1977 Mar 11;195(4282):996–998. doi: 10.1126/science.841325. [DOI] [PubMed] [Google Scholar]
  3. Allen D. G., Eisner D. A., Lab M. J., Orchard C. H. The effects of low sodium solutions on intracellular calcium concentration and tension in ferret ventricular muscle. J Physiol. 1983 Dec;345:391–407. doi: 10.1113/jphysiol.1983.sp014984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Allen D. G., Jewell B. R., Wood E. H. Studies of the contractility of mammalian myocardium at low rates of stimulation. J Physiol. 1976 Jan;254(1):1–17. doi: 10.1113/jphysiol.1976.sp011217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Barcenas-Ruiz L., Wier W. G. Voltage dependence of intracellular [Ca2+]i transients in guinea pig ventricular myocytes. Circ Res. 1987 Jul;61(1):148–154. doi: 10.1161/01.res.61.1.148. [DOI] [PubMed] [Google Scholar]
  6. Beeler G. W., Jr, Reuter H. The relation between membrane potential, membrane currents and activation of contraction in ventricular myocardial fibres. J Physiol. 1970 Mar;207(1):211–229. doi: 10.1113/jphysiol.1970.sp009057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bers D. M., MacLeod K. T. Cumulative depletions of extracellular calcium in rabbit ventricular muscle monitored with calcium-selective microelectrodes. Circ Res. 1986 Jun;58(6):769–782. doi: 10.1161/01.res.58.6.769. [DOI] [PubMed] [Google Scholar]
  8. Blatter L. A., McGuigan J. A. Free intracellular magnesium concentration in ferret ventricular muscle measured with ion selective micro-electrodes. Q J Exp Physiol. 1986 Jul;71(3):467–473. doi: 10.1113/expphysiol.1986.sp003005. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Bridge J. H. Relationships between the sarcoplasmic reticulum and sarcolemmal calcium transport revealed by rapidly cooling rabbit ventricular muscle. J Gen Physiol. 1986 Oct;88(4):437–473. doi: 10.1085/jgp.88.4.437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cannell M. B., Berlin J. R., Lederer W. J. Effect of membrane potential changes on the calcium transient in single rat cardiac muscle cells. Science. 1987 Dec 4;238(4832):1419–1423. doi: 10.1126/science.2446391. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Clusin W. T. Do caffeine and metabolic inhibitors increase free calcium in the heart? Interpretation of conflicting intracellular calcium measurements. J Mol Cell Cardiol. 1985 Mar;17(3):213–220. doi: 10.1016/s0022-2828(85)80004-3. [DOI] [PubMed] [Google Scholar]
  14. Eisner D. A., Valdeolmillos M. The mechanism of the increase of tonic tension produced by caffeine in sheep cardiac Purkinje fibres. J Physiol. 1985 Jul;364:313–326. doi: 10.1113/jphysiol.1985.sp015747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Fabiato A. Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum. Am J Physiol. 1983 Jul;245(1):C1–14. doi: 10.1152/ajpcell.1983.245.1.C1. [DOI] [PubMed] [Google Scholar]
  16. Fabiato A. Effects of ryanodine in skinned cardiac cells. Fed Proc. 1985 Dec;44(15):2970–2976. [PubMed] [Google Scholar]
  17. Hansford R. G., Lakatta E. G. Ryanodine releases calcium from sarcoplasmic reticulum in calcium-tolerant rat cardiac myocytes. J Physiol. 1987 Sep;390:453–467. doi: 10.1113/jphysiol.1987.sp016711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hilgemann D. W. Extracellular calcium transients and action potential configuration changes related to post-stimulatory potentiation in rabbit atrium. J Gen Physiol. 1986 May;87(5):675–706. doi: 10.1085/jgp.87.5.675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Isenberg G. Ca entry and contraction as studied in isolated bovine ventricular myocytes. Z Naturforsch C. 1982 May-Jun;37(5-6):502–512. doi: 10.1515/znc-1982-5-623. [DOI] [PubMed] [Google Scholar]
  20. Jundt H., Porzig H., Reuter H., Stucki J. W. The effect of substances releasing intracellular calcium ions on sodium-dependent calcium efflux from guinea-pig auricles. J Physiol. 1975 Mar;246(1):229–253. doi: 10.1113/jphysiol.1975.sp010888. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kitazawa T. Effect of extracellular calcium on contractile activation in guinea-pig ventricular muscle. J Physiol. 1984 Oct;355:635–659. doi: 10.1113/jphysiol.1984.sp015443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Konishi M., Kurihara S. Effects of caffeine on intracellular calcium concentrations in frog skeletal muscle fibres. J Physiol. 1987 Feb;383:269–283. doi: 10.1113/jphysiol.1987.sp016408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kurihara S., Sakai T. Effects of rapid cooling on mechanical and electrical responses in ventricular muscle of guinea-pig. J Physiol. 1985 Apr;361:361–378. doi: 10.1113/jphysiol.1985.sp015650. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. London B., Krueger J. W. Contraction in voltage-clamped, internally perfused single heart cells. J Gen Physiol. 1986 Oct;88(4):475–505. doi: 10.1085/jgp.88.4.475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Marban E., Wier W. G. Ryanodine as a tool to determine the contributions of calcium entry and calcium release to the calcium transient and contraction of cardiac Purkinje fibers. Circ Res. 1985 Jan;56(1):133–138. doi: 10.1161/01.res.56.1.133. [DOI] [PubMed] [Google Scholar]
  26. Reuter H. Exchange of calcium ions in the mammalian myocardium. Mechanisms and physiological significance. Circ Res. 1974 May;34(5):599–605. doi: 10.1161/01.res.34.5.599. [DOI] [PubMed] [Google Scholar]
  27. Ringer S. A further Contribution regarding the influence of the different Constituents of the Blood on the Contraction of the Heart. J Physiol. 1883 Jan;4(1):29–42.3. doi: 10.1113/jphysiol.1883.sp000120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Smith G. L., Allen D. G. Effects of metabolic blockade on intracellular calcium concentration in isolated ferret ventricular muscle. Circ Res. 1988 Jun;62(6):1223–1236. doi: 10.1161/01.res.62.6.1223. [DOI] [PubMed] [Google Scholar]
  29. Weber A., Herz R. The relationship between caffeine contracture of intact muscle and the effect of caffeine on reticulum. J Gen Physiol. 1968 Nov;52(5):750–759. doi: 10.1085/jgp.52.5.750. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wendt I. R., Stephenson D. G. Effects of caffeine on Ca-activated force production in skinned cardiac and skeletal muscle fibres of the rat. Pflugers Arch. 1983 Aug;398(3):210–216. doi: 10.1007/BF00657153. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Wier W. G., Yue D. T., Marban E. Effects of ryanodine on intracellular Ca2+ transients in mammalian cardiac muscle. Fed Proc. 1985 Dec;44(15):2989–2993. [PubMed] [Google Scholar]

Articles from The Journal of General Physiology are provided here courtesy of The Rockefeller University Press

RESOURCES