Skip to main content
NCBI home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1984 Oct;355:605–618. doi: 10.1113/jphysiol.1984.sp015441

The effects of caffeine on tension development and intracellular calcium transients in rat ventricular muscle.

M Konishi, S Kurihara, T Sakai
PMCID: PMC1193513  PMID: 6492005

Abstract

The effects of caffeine on tension and intracellular [Ca2+] were investigated in rat ventricular muscle using the Ca2+-sensitive photoprotein, aequorin. Contracture was induced by rapid application of 0.5-10 mM-caffeine solution at 20 degrees C. In normal Tyrode solution at 8 degrees C, or in Na+-deficient solution in which Na+ was isotonically replaced by sucrose, peak tension of caffeine contracture was potentiated and relaxation was prolonged. Caffeine contracture could not be induced immediately after a prior contracture. Repriming time was 10 min in Tyrode solution, and was much shorter in Na+-deficient solution or in high-K+ solution containing 105.9 mM-K+. Caffeine prolonged the plateau of action potential dose dependently. At low temperature, prolongation of the plateau phase by caffeine was more marked. Twitch tension showed a triphasic change after application of caffeine; peak tension transiently increased in a potentiating phase (P phase), and then decreased below control level in an inhibitory phase (I phase) followed by gradual recovery in a recovery phase (R phase). The effects of caffeine on the Ca2+ transients during a twitch were also complex, depending on time after application and dose of caffeine. In low caffeine concentration (below 0.5 mM) the peak of the Ca2+ transient was potentiated in the I phase, although the peak tension was suppressed. At high concentration (above 3 mM) the peaks of both the Ca2+ transient and twitch tension were suppressed. In every concentration of caffeine tested (0.1-5 mM), time to the Ca2+ transient and twitch tension peaks was prolonged, and the falling phases of both were delayed. Caffeine might release Ca2+ from intracellular store(s) and enhance the slow inward current. The Ca2+ transient obtained in this study clearly indicate that the prolonged time to peak tension in the presence of caffeine is due to the slow rise of intracellular [Ca2+] and prolonged time to peak of the Ca2+ transient. It is also quite possible that caffeine modulates the Ca2+ sensitivity of a contractile system in dose- and time-dependent manners.

Full text

PDF
605

Selected References

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

  1. AXELSSON J., THESLEFF S. Activation of the contractile mechanism in striated muscle. Acta Physiol Scand. 1958 Oct 28;44(1):55–66. doi: 10.1111/j.1748-1716.1958.tb01608.x. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. 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]
  4. Allen D. G., Kurihara S. The effects of muscle length on intracellular calcium transients in mammalian cardiac muscle. J Physiol. 1982 Jun;327:79–94. doi: 10.1113/jphysiol.1982.sp014221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blayney L., Thomas H., Muir J., Henderson A. Action of caffeine on calcium transport by isolated fractions of myofibrils, mitochondria, and sarcoplasmic reticulum from rabbit heart. Circ Res. 1978 Oct;43(4):520–526. doi: 10.1161/01.res.43.4.520. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Blinks J. R., Wier W. G., Hess P., Prendergast F. G. Measurement of Ca2+ concentrations in living cells. Prog Biophys Mol Biol. 1982;40(1-2):1–114. doi: 10.1016/0079-6107(82)90011-6. [DOI] [PubMed] [Google Scholar]
  8. Bodem R., Sonnenblick E. H. Mechanical activity of mammalian heart muscle: variable onset, species differences, and the effect of caffeine. Am J Physiol. 1975 Jan;228(1):250–261. doi: 10.1152/ajplegacy.1975.228.1.250. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Eisner D. A., Lederer W. J., Noble D. Caffeine and tetracaine abolish the slow inward calcium current in sheep cardiac Purkinje fibres [proceedings]. J Physiol. 1979 Aug;293:76P–77P. [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Flitney F. W., Singh J. Inotropic responses of the frog ventricle to adenosine triphosphate and related changes in endogenous cyclic nucleotides. J Physiol. 1980 Jul;304:21–42. doi: 10.1113/jphysiol.1980.sp013307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. 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]
  16. McClellan G. B., Winegrad S. The regulation of the calcium sensitivity of the contractile system in mammalian cardiac muscle. J Gen Physiol. 1978 Dec;72(6):737–764. doi: 10.1085/jgp.72.6.737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mope L., McClellan G. B., Winegrad S. Calcium sensitivity of the contractile system and phosphorylation of troponin in hyperpermeable cardiac cells. J Gen Physiol. 1980 Mar;75(3):271–282. doi: 10.1085/jgp.75.3.271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. 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]
  21. Poledna J., Morad M. Effect of caffeine on the birefringence signal in single skeletal muscle fibers and mammalian heart. Possible mechanism of action. Pflugers Arch. 1983 May;397(3):184–189. doi: 10.1007/BF00584355. [DOI] [PubMed] [Google Scholar]
  22. Sakai T., Geffner E. S., Sandow A. Caffeine contracture in muscle with disrupted transverse tubules. Am J Physiol. 1971 Mar;220(3):712–717. doi: 10.1152/ajplegacy.1971.220.3.712. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. 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]
  25. Yamamoto K., Ohtsuki I. Effect of phosphorylation of porcine cardiac troponin I by 3':5'-cyclic AMP-dependent protein kinase on the actomyosin ATPase activity. J Biochem. 1982 May;91(5):1669–1677. doi: 10.1093/oxfordjournals.jbchem.a133858. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES