Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1993 May;109(1):157–163. doi: 10.1111/j.1476-5381.1993.tb13546.x

Effects of MS-551, a new class III antiarrhythmic drug, on action potential and membrane currents in rabbit ventricular myocytes.

H Nakaya 1, N Tohse 1, Y Takeda 1, M Kanno 1
PMCID: PMC2175592  PMID: 7684298

Abstract

1. Electrophysiological effects of MS-551, a new class III antiarrhythmic drug, were examined and compared with those of (+)-sotalol in rabbit ventricular cells. 2. In rabbit ventricular muscles stimulated at 1.0 Hz, MS-551 (0.1-10 microM) and (+)-sotalol (3-100 microM) prolonged action potential duration (APD) and effective refractory period without affecting the maximum upstroke velocity of phase 0 depolarization (Vmax). The class III effect of MS-551 was approximately 30 times more potent than that of (+)-sotalol. 3. Class III effects of MS-551 and (+)-sotalol showed reverse use-dependence, i.e., a greater prolongation of APD at a longer cycle length. 4. In rabbit isolated ventricular cells, 3 microM MS-551 and 100 microM sotalol inhibited the delayed rectifier potassium current (IK) which was activated at more positive potentials than -50 mV and saturated around +20 mV. 5. MS-551 at a higher concentration of 10 microM decreased the transient outward current (Ito) and the inward rectifier potassium current (IK1) although 100 microM sotalol failed to inhibit these currents. 6. MS-551 is a non-specific class III drug which can inhibit three voltage-gated K+ channels in rabbit ventricular cells.

Full text

PDF
158

Selected References

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

  1. Apkon M., Nerbonne J. M. Alpha 1-adrenergic agonists selectively suppress voltage-dependent K+ current in rat ventricular myocytes. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8756–8760. doi: 10.1073/pnas.85.22.8756. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arena J. P., Kass R. S. Block of heart potassium channels by clofilium and its tertiary analogs: relationship between drug structure and type of channel blocked. Mol Pharmacol. 1988 Jul;34(1):60–66. [PubMed] [Google Scholar]
  3. Ben-David J., Zipes D. P. Alpha-adrenoceptor stimulation and blockade modulates cesium-induced early afterdepolarizations and ventricular tachyarrhythmias in dogs. Circulation. 1990 Jul;82(1):225–233. doi: 10.1161/01.cir.82.1.225. [DOI] [PubMed] [Google Scholar]
  4. Black S. C., Chi L. G., Mu D. X., Lucchesi B. R. The antifibrillatory actions of UK-68,798, a class III antiarrhythmic agent. J Pharmacol Exp Ther. 1991 Aug;258(2):416–423. [PubMed] [Google Scholar]
  5. Carlsson L., Almgren O., Duker G. QTU-prolongation and torsades de pointes induced by putative class III antiarrhythmic agents in the rabbit: etiology and interventions. J Cardiovasc Pharmacol. 1990 Aug;16(2):276–285. doi: 10.1097/00005344-199008000-00014. [DOI] [PubMed] [Google Scholar]
  6. Chi L. G., Mu D. X., Lucchesi B. R. Electrophysiology and antiarrhythmic actions of E-4031 in the experimental animal model of sudden coronary death. J Cardiovasc Pharmacol. 1991 Feb;17(2):285–295. doi: 10.1097/00005344-199102000-00015. [DOI] [PubMed] [Google Scholar]
  7. Dukes I. D., Cleemann L., Morad M. Tedisamil blocks the transient and delayed rectifier K+ currents in mammalian cardiac and glial cells. J Pharmacol Exp Ther. 1990 Aug;254(2):560–569. [PubMed] [Google Scholar]
  8. Escande D., Coulombe A., Faivre J. F., Deroubaix E., Coraboeuf E. Two types of transient outward currents in adult human atrial cells. Am J Physiol. 1987 Jan;252(1 Pt 2):H142–H148. doi: 10.1152/ajpheart.1987.252.1.H142. [DOI] [PubMed] [Google Scholar]
  9. Fedida D., Braun A. P., Giles W. R. Alpha 1-adrenoceptors reduce background K+ current in rabbit ventricular myocytes. J Physiol. 1991 Sep;441:673–684. doi: 10.1113/jphysiol.1991.sp018772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fedida D., Giles W. R. Regional variations in action potentials and transient outward current in myocytes isolated from rabbit left ventricle. J Physiol. 1991 Oct;442:191–209. doi: 10.1113/jphysiol.1991.sp018789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fedida D., Shimoni Y., Giles W. R. A novel effect of norepinephrine on cardiac cells is mediated by alpha 1-adrenoceptors. Am J Physiol. 1989 May;256(5 Pt 2):H1500–H1504. doi: 10.1152/ajpheart.1989.256.5.H1500. [DOI] [PubMed] [Google Scholar]
  12. Friedman L. M. Can chronic antidysrhythmic treatment prevent sudden death? Eur Heart J. 1984 Sep;5 (Suppl B):99–101. doi: 10.1093/eurheartj/5.suppl_b.99. [DOI] [PubMed] [Google Scholar]
  13. Giles W. R., Imaizumi Y. Comparison of potassium currents in rabbit atrial and ventricular cells. J Physiol. 1988 Nov;405:123–145. doi: 10.1113/jphysiol.1988.sp017325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gwilt M., Arrowsmith J. E., Blackburn K. J., Burges R. A., Cross P. E., Dalrymple H. W., Higgins A. J. UK-68,798: a novel, potent and highly selective class III antiarrhythmic agent which blocks potassium channels in cardiac cells. J Pharmacol Exp Ther. 1991 Jan;256(1):318–324. [PubMed] [Google Scholar]
  15. Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
  16. Hiraoka M., Kawano S. Calcium-sensitive and insensitive transient outward current in rabbit ventricular myocytes. J Physiol. 1989 Mar;410:187–212. doi: 10.1113/jphysiol.1989.sp017528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hondeghem L. M., Snyders D. J. Class III antiarrhythmic agents have a lot of potential but a long way to go. Reduced effectiveness and dangers of reverse use dependence. Circulation. 1990 Feb;81(2):686–690. doi: 10.1161/01.cir.81.2.686. [DOI] [PubMed] [Google Scholar]
  18. Isenberg G., Klockner U. Calcium tolerant ventricular myocytes prepared by preincubation in a "KB medium". Pflugers Arch. 1982 Oct;395(1):6–18. doi: 10.1007/BF00584963. [DOI] [PubMed] [Google Scholar]
  19. Kameyama M., Kiyosue T., Soejima M. Single channel analysis of the inward rectifier K current in the rabbit ventricular cells. Jpn J Physiol. 1983;33(6):1039–1056. doi: 10.2170/jjphysiol.33.1039. [DOI] [PubMed] [Google Scholar]
  20. Kamiya J., Ishii M., Katakami T. Antiarrhythmic effects of MS-551, a new class III antiarrhythmic agent, on canine models of ventricular arrhythmia. Jpn J Pharmacol. 1992 Feb;58(2):107–115. doi: 10.1254/jjp.58.107. [DOI] [PubMed] [Google Scholar]
  21. Katoh H., Ogawa S., Furuno I., Sato Y., Yoh S., Saeki K., Nakamura Y. Electrophysiologic effects of E-4031, a class III antiarrhythmic agent, on re-entrant ventricular arrhythmias in a canine 7-day-old myocardial infarction model. J Pharmacol Exp Ther. 1990 Jun;253(3):1077–1082. [PubMed] [Google Scholar]
  22. Komeichi K., Tohse N., Nakaya H., Shimizu M., Zhu M. Y., Kanno M. Effects of N-acetylprocainamide and sotalol on ion currents in isolated guinea-pig ventricular myocytes. Eur J Pharmacol. 1990 Oct 23;187(3):313–322. doi: 10.1016/0014-2999(90)90358-d. [DOI] [PubMed] [Google Scholar]
  23. Lynch J. J., Coskey L. A., Montgomery D. G., Lucchesi B. R. Prevention of ventricular fibrillation by dextrorotatory sotalol in a conscious canine model of sudden coronary death. Am Heart J. 1985 May;109(5 Pt 1):949–958. doi: 10.1016/0002-8703(85)90234-0. [DOI] [PubMed] [Google Scholar]
  24. Lynch J. J., Jr, Heaney L. A., Wallace A. A., Gehret J. R., Selnick H. G., Stein R. B. Suppression of lethal ischemic ventricular arrhythmias by the class III agent E4031 in a canine model of previous myocardial infarction. J Cardiovasc Pharmacol. 1990 May;15(5):764–775. doi: 10.1097/00005344-199005000-00012. [DOI] [PubMed] [Google Scholar]
  25. Lynch J. J., Wilber D. J., Montgomery D. G., Hsieh T. M., Patterson E., Lucchesi B. R. Antiarrhythmic and antifibrillatory actions of the levo- and dextrorotatory isomers of sotalol. J Cardiovasc Pharmacol. 1984 Nov-Dec;6(6):1132–1141. [PubMed] [Google Scholar]
  26. Matsuura H., Ehara T., Imoto Y. An analysis of the delayed outward current in single ventricular cells of the guinea-pig. Pflugers Arch. 1987 Dec;410(6):596–603. doi: 10.1007/BF00581319. [DOI] [PubMed] [Google Scholar]
  27. Nakaya H., Tohse N., Kanno M. Electrophysiological derangements induced by lipid peroxidation in cardiac tissue. Am J Physiol. 1987 Nov;253(5 Pt 2):H1089–H1097. doi: 10.1152/ajpheart.1987.253.5.H1089. [DOI] [PubMed] [Google Scholar]
  28. Roden D. M., Bennett P. B., Snyders D. J., Balser J. R., Hondeghem L. M. Quinidine delays IK activation in guinea pig ventricular myocytes. Circ Res. 1988 May;62(5):1055–1058. doi: 10.1161/01.res.62.5.1055. [DOI] [PubMed] [Google Scholar]
  29. Sanguinetti M. C., Jurkiewicz N. K. Two components of cardiac delayed rectifier K+ current. Differential sensitivity to block by class III antiarrhythmic agents. J Gen Physiol. 1990 Jul;96(1):195–215. doi: 10.1085/jgp.96.1.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Shibasaki T. Conductance and kinetics of delayed rectifier potassium channels in nodal cells of the rabbit heart. J Physiol. 1987 Jun;387:227–250. doi: 10.1113/jphysiol.1987.sp016571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Shibata E. F., Drury T., Refsum H., Aldrete V., Giles W. Contributions of a transient outward current to repolarization in human atrium. Am J Physiol. 1989 Dec;257(6 Pt 2):H1773–H1781. doi: 10.1152/ajpheart.1989.257.6.H1773. [DOI] [PubMed] [Google Scholar]
  32. Shimoni Y., Clark R. B., Giles W. R. Role of an inwardly rectifying potassium current in rabbit ventricular action potential. J Physiol. 1992 Mar;448:709–727. doi: 10.1113/jphysiol.1992.sp019066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Singh B. N., Sarma J. S., Zhang Z. H., Takanaka C. Controlling cardiac arrhythmias by lengthening repolarization: rationale from experimental findings and clinical considerations. Ann N Y Acad Sci. 1992 Jan 27;644:187–209. doi: 10.1111/j.1749-6632.1992.tb31011.x. [DOI] [PubMed] [Google Scholar]
  34. Tohse N. Calcium-sensitive delayed rectifier potassium current in guinea pig ventricular cells. Am J Physiol. 1990 Apr;258(4 Pt 2):H1200–H1207. doi: 10.1152/ajpheart.1990.258.4.H1200. [DOI] [PubMed] [Google Scholar]
  35. Tohse N., Nakaya H., Hattori Y., Endou M., Kanno M. Inhibitory effect mediated by alpha 1-adrenoceptors on transient outward current in isolated rat ventricular cells. Pflugers Arch. 1990 Feb;415(5):575–581. doi: 10.1007/BF02583508. [DOI] [PubMed] [Google Scholar]
  36. Zuanetti G., Corr P. B. Antiarrhythmic efficacy of a new class III agent, UK-68,798, during chronic myocardial infarction: evaluation using three-dimensional mapping. J Pharmacol Exp Ther. 1991 Jan;256(1):325–334. [PubMed] [Google Scholar]

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

RESOURCES