Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1993 Mar;108(3):812–818. doi: 10.1111/j.1476-5381.1993.tb12883.x

Use-dependent block of Ca2+ current by moricizine in guinea-pig ventricular myocytes: a possible ionic mechanism of action potential shortening.

T Yamane 1, A Sunami 1, T Sawanobori 1, M Hiraoka 1
PMCID: PMC1908024  PMID: 8385537

Abstract

1. Whole cell patch clamp techniques were used to study the effects of moricizine on membrane currents in guinea-pig ventricular myocytes. 2. Application of moricizine caused reversible depression of the time-dependent outward K+ current. 3. The Na+/Ca2+ exchange current was not directly affected by moricizine. 4. Although moricizine hardly affected the L-type Ca2+ current when cells were stimulated at a frequency of 0.1 Hz, it suppressed the current at depolarized holding potentials in a use-dependent manner at 1 Hz. 5. Developments of use-dependent block of the Ca2+ current in the presence of moricizine were best expressed by two exponentials. Binding to both activated and inactivated states of the Ca2+ channel were supported from the binding kinetics study. 6. We concluded that moricizine suppressed the L-type Ca2+ current in a use-dependent manner and this might explain, at least in part, action potential shortening by the drug.

Full text

PDF
812

Selected References

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

  1. Bean B. P. Two kinds of calcium channels in canine atrial cells. Differences in kinetics, selectivity, and pharmacology. J Gen Physiol. 1985 Jul;86(1):1–30. doi: 10.1085/jgp.86.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Carmeliet E., Saikawa T. Shortening of the action potential and reduction of pacemaker activity by lidocaine, quinidine, and procainamide in sheep cardiac purkinje fibers. An effect on Na or K currents? Circ Res. 1982 Feb;50(2):257–272. doi: 10.1161/01.res.50.2.257. [DOI] [PubMed] [Google Scholar]
  3. Dangman K. H., Hoffman B. F. Antiarrhythmic effects of ethmozin in cardiac Purkinje fibers: suppression of automaticity and abolition of triggering. J Pharmacol Exp Ther. 1983 Dec;227(3):578–586. [PubMed] [Google Scholar]
  4. Danilo P., Jr, Langan W. B., Rosen M. R., Hoffman B. F. Effects of the phenothiazine analog, EN-313, on ventricular arrhythmias in the dog. Eur J Pharmacol. 1977 Sep 15;45(2):127–139. doi: 10.1016/0014-2999(77)90082-6. [DOI] [PubMed] [Google Scholar]
  5. Fitton A., Buckley M. T. Moricizine. A review of its pharmacological properties, and therapeutic efficacy in cardiac arrhythmias. Drugs. 1990 Jul;40(1):138–167. doi: 10.2165/00003495-199040010-00007. [DOI] [PubMed] [Google Scholar]
  6. Hewett K., Gessman L., Rosen M. R. Effects of procaine amide, quinidine and ethmozin on delayed afterdepolarizations. Eur J Pharmacol. 1983 Dec 9;96(1-2):21–28. doi: 10.1016/0014-2999(83)90524-1. [DOI] [PubMed] [Google Scholar]
  7. Hirano Y., Hiraoka M. Barium-induced automatic activity in isolated ventricular myocytes from guinea-pig hearts. J Physiol. 1988 Jan;395:455–472. doi: 10.1113/jphysiol.1988.sp016929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hiraoka M., Sawada K., Kawano S. Effects of quinidine on plateau currents of guinea-pig ventricular myocytes. J Mol Cell Cardiol. 1986 Oct;18(10):1097–1106. doi: 10.1016/s0022-2828(86)80296-6. [DOI] [PubMed] [Google Scholar]
  9. Hondeghem L. M., Katzung B. G. Time- and voltage-dependent interactions of antiarrhythmic drugs with cardiac sodium channels. Biochim Biophys Acta. 1977 Nov 14;472(3-4):373–398. doi: 10.1016/0304-4157(77)90003-x. [DOI] [PubMed] [Google Scholar]
  10. January C. T., Riddle J. M., Salata J. J. A model for early afterdepolarizations: induction with the Ca2+ channel agonist Bay K 8644. Circ Res. 1988 Mar;62(3):563–571. doi: 10.1161/01.res.62.3.563. [DOI] [PubMed] [Google Scholar]
  11. Kimura J., Miyamae S., Noma A. Identification of sodium-calcium exchange current in single ventricular cells of guinea-pig. J Physiol. 1987 Mar;384:199–222. doi: 10.1113/jphysiol.1987.sp016450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kiyosue T., Arita M. Late sodium current and its contribution to action potential configuration in guinea pig ventricular myocytes. Circ Res. 1989 Feb;64(2):389–397. doi: 10.1161/01.res.64.2.389. [DOI] [PubMed] [Google Scholar]
  13. Lee J. H., Rosen M. R. Use-dependent actions and effects on transmembrane action potentials of flecainide, encainide, and ethmozine in canine Purkinje fibers. J Cardiovasc Pharmacol. 1991 Aug;18(2):285–292. doi: 10.1097/00005344-199108000-00016. [DOI] [PubMed] [Google Scholar]
  14. Makielski J. C., Undrovinas A. I., Hanck D. A., Sheets M. F., Nesterenko V. V., Alpert L. A., Rosenshtraukh L. V., Fozzard H. A. Use-dependent block of sodium current by ethmozin in voltage-clamped internally perfused canine cardiac Purkinje cells. J Mol Cell Cardiol. 1988 Mar;20(3):255–265. doi: 10.1016/s0022-2828(88)80058-0. [DOI] [PubMed] [Google Scholar]
  15. Mann H. J. Moricizine: a new class I antiarrhythmic. Clin Pharm. 1990 Nov;9(11):842–852. [PubMed] [Google Scholar]
  16. Rosenshtraukh L. V., Anyukhovsky E. P., Nesterenko V. V., Undrovinas A. I., Shugushev K. Kh, Portnoy V. F., Burnashev N. A. Electrophysiologic aspects of moricizine HCl. Am J Cardiol. 1987 Oct 16;60(11):27F–34F. doi: 10.1016/0002-9149(87)90717-x. [DOI] [PubMed] [Google Scholar]
  17. Ruffy R., Rozenshtraukh L. V., Elharrar V., Zipes D. P. Electrophysiological effects of ethmozin on canine myocardium. Cardiovasc Res. 1979 Jun;13(6):354–363. doi: 10.1093/cvr/13.6.354. [DOI] [PubMed] [Google Scholar]
  18. Salata J. J., Wasserstrom J. A. Effects of quinidine on action potentials and ionic currents in isolated canine ventricular myocytes. Circ Res. 1988 Feb;62(2):324–337. doi: 10.1161/01.res.62.2.324. [DOI] [PubMed] [Google Scholar]
  19. Scamps F., Undrovinas A., Vassort G. Inhibition of ICa in single frog cardiac cells by quinidine, flecainide, ethmozin, and ethacizin. Am J Physiol. 1989 Mar;256(3 Pt 1):C549–C559. doi: 10.1152/ajpcell.1989.256.3.C549. [DOI] [PubMed] [Google Scholar]
  20. Sunami A., Fan Z., Nitta J., Hiraoka M. Two components of use-dependent block of Na+ current by disopyramide and lidocaine in guinea pig ventricular myocytes. Circ Res. 1991 Mar;68(3):653–661. doi: 10.1161/01.res.68.3.653. [DOI] [PubMed] [Google Scholar]
  21. Tsuji Y., Nishimura M., Osada M., Watanabe Y. Membrane action of ethmozin on normoxic and hypoxic canine Purkinje fibers. J Cardiovasc Pharmacol. 1983 Nov-Dec;5(6):961–967. doi: 10.1097/00005344-198311000-00008. [DOI] [PubMed] [Google Scholar]
  22. Vaughan Williams E. M. Classification of the antiarrhythmic action of moricizine. J Clin Pharmacol. 1991 Mar;31(3):216–221. doi: 10.1002/j.1552-4604.1991.tb04964.x. [DOI] [PubMed] [Google Scholar]
  23. Yatani A., Wilson D. L., Brown A. M. Recovery of Ca currents from inactivation: the roles of Ca influx, membrane potential, and cellular metabolism. Cell Mol Neurobiol. 1983 Dec;3(4):381–395. doi: 10.1007/BF00734718. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES