Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1981 Sep;74(1):29–37. doi: 10.1111/j.1476-5381.1981.tb09952.x

Electromechanical effects of anthopleurin-A (AP-A) on rabbit ventricular muscle: influence of driving frequency, calcium antagonists, tetrodotoxin, lidocaine and ryanodine

Itsuo Kodama, Shoji Shibata, Junji Toyama, Kazuo Yamada
PMCID: PMC2071880  PMID: 7272601

Abstract

1 Anthopleurin-A (AP-A 5 × 10-9 M, 1 × 10-8 M) caused a prolongation of action potential duration (APD) and an increase of contractile force in rabbit isolated ventricular muscle preparations.

2 The prolongation of APD and the positive inotropic effect of AP-A (1 × 10-8 M) were augmented by lowering the driving frequency from 2.0 to 0.2 Hz, resulting in an apparent negative staircase of contractile force in this frequency range. When the preparation was driven at an extremely low frequency (0.017 Hz), AP-A did not increase the contractile force, but caused a considerable prolongation of APD.

3 Verapamil (1 × 10-6 M) and nifedipine (1 × 10-6 M) had no apparent influence on the APD prolongation by AP-A (5 × 10-9 M, 1 × 10-8 M). The positive inotropic effect of AP-A was also relatively well maintained even in the presence of these calcium antagonistic drugs when the preparation was driven at a lower frequency (0.2 Hz).

4 Tetrodotoxin (TTX 2 × 10-6 M) and lidocaine (1 × 10-4 M) markedly inhibited both the APD prolongation and the positive inotropic effect of AP-A (1 × 10-8 M).

5 In the presence of ryanodine (2 × 10-6 M), an agent which is known to interfere with calcium release from the intracellular activator pool, AP-A (1 × 10-8 M) failed to cause its positive inotropic effect in spite of the marked prolongation of APD.

6 These results suggest that the effects of AP-A on cardiac muscle are primarily mediated by the fast sodium inward current. Thus, delayed inactivation of sodium inward current may cause APD prolongation, and probably induces an alteration of intracellular calcium kinetics reflected by an increase of contractile force.

Full text

PDF
29

Selected References

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

  1. 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]
  2. Blair R. W., Peterson D. F., Bishop V. S. The effects of anthopleurin-A on cardiac dynamics in conscious dogs. J Pharmacol Exp Ther. 1978 Nov;207(2):271–276. [PubMed] [Google Scholar]
  3. 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]
  4. Edman K. A., Jóhannsson M. The contractile state of rabbit papillary muscle in relation to stimulation frequency. J Physiol. 1976 Jan;254(3):565–581. doi: 10.1113/jphysiol.1976.sp011247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Honerjäger P., Reiter M. The relation between the effects of veratridine on action potential and contraction in mammalian ventricular myocardium. Naunyn Schmiedebergs Arch Pharmacol. 1975;289(1):1–28. doi: 10.1007/BF00498026. [DOI] [PubMed] [Google Scholar]
  7. Horackova M., Vassort G. Ionic mechanism of inotropic effect of veratrine on frog heart. Pflugers Arch. 1973 Jul 31;341(4):281–284. doi: 10.1007/BF01023669. [DOI] [PubMed] [Google Scholar]
  8. Jones L. R., Besch H. R., Jr, Sutko J. L., Willerson J. T. Ryanodine-induced stimulation of net Ca++ uptake by cardiac sarcoplasmic reticulum vesicles. J Pharmacol Exp Ther. 1979 Apr;209(1):48–55. [PubMed] [Google Scholar]
  9. Kodama I., Toyama J., Shibata S., Norton T. R. Electrical and mechanical effects of anthopleurin-A, a polypeptide from a sea anemone, on isolated rabbit ventricular muscle under conditions of hypoxia and glucose-free medium. J Cardiovasc Pharmacol. 1981 Jan-Feb;3(1):75–86. doi: 10.1097/00005344-198101000-00007. [DOI] [PubMed] [Google Scholar]
  10. Low P. A., Wu C. H., Narahashi T. The effect of anthopleurin-A on crayfish giant axon. J Pharmacol Exp Ther. 1979 Sep;210(3):417–421. [PubMed] [Google Scholar]
  11. Norton T. R., Shibata S., Kashiwagi M., Bentley J. Isolation and characterization of the cardiotonic polypeptide anthopleurin-A from the sea anemone Anthopleura xanthogrammica. J Pharm Sci. 1976 Sep;65(9):1368–1374. doi: 10.1002/jps.2600650927. [DOI] [PubMed] [Google Scholar]
  12. Ravens U. Electromechanical studies of an Anemonia sulcata toxin in mammalian cardiac muscle. Naunyn Schmiedebergs Arch Pharmacol. 1976 Dec;296(1):73–78. doi: 10.1007/BF00498842. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Scriabine A., Van Arman C. G., Morgan G., Morris A. A., Bennett C. D., Bohidar N. R. Cardiotonic effects of anthopleurin-A, a polypeptide from a sea anemone. J Cardiovasc Pharmacol. 1979 Sep-Oct;1(5):571–583. doi: 10.1097/00005344-197909000-00009. [DOI] [PubMed] [Google Scholar]
  15. Shibata S., Dunn D. F., Kuchii M., Kashiwagi M., Norton T. R. Cardiac stimulant action of extracts of coelenterates on rat atria. J Pharm Sci. 1974 Aug;63(8):1332–1333. doi: 10.1002/jps.2600630845. [DOI] [PubMed] [Google Scholar]
  16. Shibata S., Izumi T., Seriguchi D. G., Norton T. R. Further studies on the positive inotropic effect of the polypeptide anthopleurin-A from a sea anemone. J Pharmacol Exp Ther. 1978 Jun;205(3):683–692. [PubMed] [Google Scholar]
  17. Shibata S., Norton T. R., Izumi T., Matsuo T., Katsuki S. A polypeptide (AP-A) from sea anemone (Anthopleura xanthogrammica) with potent positive inotropic action. J Pharmacol Exp Ther. 1976 Nov;199(2):298–309. [PubMed] [Google Scholar]
  18. Shimizu T., Iwamura N., Toyama J., Yamada K., Shibata S. Effect of cardiotonic polypeptide anthopleurin-A on canine Purkinje and ventricular muscle fibers. Eur J Pharmacol. 1979 Jun;56(1-2):7–13. doi: 10.1016/0014-2999(79)90426-6. [DOI] [PubMed] [Google Scholar]
  19. Sutko J. L., Willerson J. T., Templeton G. H., Jones L. R., Besch H. R., Jr Ryanodine: its alterations of cat papillary muscle contractile state and responsiveness to inotropic interventions and a suggested mechanism of action. J Pharmacol Exp Ther. 1979 Apr;209(1):37–47. [PubMed] [Google Scholar]
  20. Tanaka M., Hainu M., Yasunobu K. T., Norton T. R. Amino acid sequence of the Anthopleura xanthogrammica heart stimulant, anthopleurin A. Biochemistry. 1977 Jan 25;16(2):204–208. doi: 10.1021/bi00621a007. [DOI] [PubMed] [Google Scholar]
  21. Vassort G. Influence of sodium ions on the regulation of frog myocardial contractility. Pflugers Arch. 1973 Mar 30;339(3):224–240. doi: 10.1007/BF00587374. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES