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. 1992 Dec;107(4):1061–1067. doi: 10.1111/j.1476-5381.1992.tb13407.x

Blockade by antiarrhythmic drugs of glibenclamide-sensitive K+ channels in Xenopus oocytes.

H Sakuta 1, K Okamoto 1, Y Watanabe 1
PMCID: PMC1907933  PMID: 1361399

Abstract

1. The outward K+ current induced by KRN2391 (K+ channel opener) in Xenopus oocytes is blocked by glibenclamide. We have investigated the effects of various classes (I-IV) of antiarrhythmic drugs on this KRN2391-induced response. 2. All class I antiarrhythmic drugs (Na+ channel blockers) tested concentration-dependently suppressed KRN2391-induced responses with the rank order of potency (IC50 in microM), disopyramide (17.8) > aprindine (29.5) > propafenone (63.1) > ajmaline (145) > quinidine (151). Flecainide, SUN1165, lignocaine, mexiletine and procainamide were much less potent (IC50, 450- > 1000 microM) than quinidine. 3. The class II antiarrhythmic drugs (beta-blockers), timolol, (-)- and (+/-)- propranolol, and (+)- propranolol (a non-beta-blocker) inhibited KRN2391-induced K+ currents in a concentration-dependent manner with values for IC50 (microM) of 79, 131, 151 and 129, respectively, whilst butoxamine, oxprenolol, alprenolol, pindolol, nadolol, metoprolol and acebutolol were either weak (IC50, 300 microM-600 microM) or virtually inactive (IC50, > 1000 microM). 4. The class III antiarrhythmic drugs, amiodarone and (+)-sotalol scarcely affected KRN2391 responses. 5. All class IV drugs (Ca2+ antagonists) tested suppressed KRN2391-induced responses in a concentration-dependent manner with an IC50 of 6.3 microM for bepridil, 38 microM for prenylamine, 85 microM for verapamil and 135 microM for diltiazem. 6. In conclusion, antiarrhythmic drugs of classes I, II and IV potently blocked glibenclamide-sensitive K+ channels in Xenopus oocytes.

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Selected References

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

  1. Ashcroft F. M., Harrison D. E., Ashcroft S. J. Glucose induces closure of single potassium channels in isolated rat pancreatic beta-cells. 1984 Nov 29-Dec 5Nature. 312(5993):446–448. doi: 10.1038/312446a0. [DOI] [PubMed] [Google Scholar]
  2. Ashford M. L., Sturgess N. C., Trout N. J., Gardner N. J., Hales C. N. Adenosine-5'-triphosphate-sensitive ion channels in neonatal rat cultured central neurones. Pflugers Arch. 1988 Aug;412(3):297–304. doi: 10.1007/BF00582512. [DOI] [PubMed] [Google Scholar]
  3. Balser J. R., Bennett P. B., Hondeghem L. M., Roden D. M. Suppression of time-dependent outward current in guinea pig ventricular myocytes. Actions of quinidine and amiodarone. Circ Res. 1991 Aug;69(2):519–529. doi: 10.1161/01.res.69.2.519. [DOI] [PubMed] [Google Scholar]
  4. Barron E., Marshall R. J., Martorana M., Winslow E. Comparative antiarrhythmic and electrophysiological effects of drugs known to inhibit calmodulin (TFP, W7 and bepridil). Br J Pharmacol. 1986 Nov;89(3):603–612. doi: 10.1111/j.1476-5381.1986.tb11162.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carmeliet E. Electrophysiologic and voltage clamp analysis of the effects of sotalol on isolated cardiac muscle and Purkinje fibers. J Pharmacol Exp Ther. 1985 Mar;232(3):817–825. [PubMed] [Google Scholar]
  6. Cook D. L., Hales C. N. Intracellular ATP directly blocks K+ channels in pancreatic B-cells. Nature. 1984 Sep 20;311(5983):271–273. doi: 10.1038/311271a0. [DOI] [PubMed] [Google Scholar]
  7. Epstein P. M., Fiss K., Hachisu R., Andrenyak D. M. Interaction of calcium antagonists with cyclic AMP phosphodiesterases and calmodulin. Biochem Biophys Res Commun. 1982 Apr 14;105(3):1142–1149. doi: 10.1016/0006-291x(82)91089-0. [DOI] [PubMed] [Google Scholar]
  8. Escande D., Thuringer D., Leguern S., Cavero I. The potassium channel opener cromakalim (BRL 34915) activates ATP-dependent K+ channels in isolated cardiac myocytes. Biochem Biophys Res Commun. 1988 Jul 29;154(2):620–625. doi: 10.1016/0006-291x(88)90184-2. [DOI] [PubMed] [Google Scholar]
  9. Fleckenstein A. Historical overview. The calcium channel of the heart. Ann N Y Acad Sci. 1988;522:1–15. doi: 10.1111/j.1749-6632.1988.tb33337.x. [DOI] [PubMed] [Google Scholar]
  10. Haworth R. A., Goknur A. B., Berkoff H. A. Inhibition of ATP-sensitive potassium channels of adult rat heart cells by antiarrhythmic drugs. Circ Res. 1989 Oct;65(4):1157–1160. doi: 10.1161/01.res.65.4.1157. [DOI] [PubMed] [Google Scholar]
  11. Hidaka H., Asano M., Tanaka T. Activity-structure relationship of calmodulin antagonists, Naphthalenesulfonamide derivatives. Mol Pharmacol. 1981 Nov;20(3):571–578. [PubMed] [Google Scholar]
  12. Hidaka H., Yamaki T., Naka M., Tanaka T., Hayashi H., Kobayashi R. Calcium-regulated modulator protein interacting agents inhibit smooth muscle calcium-stimulated protein kinase and ATPase. Mol Pharmacol. 1980 Jan;17(1):66–72. [PubMed] [Google Scholar]
  13. Honoré E., Lazdunski M. Hormone-regulated K+ channels in follicle-enclosed oocytes are activated by vasorelaxing K+ channel openers and blocked by antidiabetic sulfonylureas. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5438–5442. doi: 10.1073/pnas.88.12.5438. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Honoré E., Lazdunski M. Two different types of channels are targets for potassium channel openers in Xenopus oocytes. FEBS Lett. 1991 Aug 5;287(1-2):75–79. doi: 10.1016/0014-5793(91)80019-y. [DOI] [PubMed] [Google Scholar]
  15. Itoh H., Ishikawa T., Hidaka H. Effects on calmodulin of bepridil, an antianginal agent. J Pharmacol Exp Ther. 1984 Sep;230(3):737–741. [PubMed] [Google Scholar]
  16. Kantor P. F., Coetzee W. A., Carmeliet E. E., Dennis S. C., Opie L. H. Reduction of ischemic K+ loss and arrhythmias in rat hearts. Effect of glibenclamide, a sulfonylurea. Circ Res. 1990 Feb;66(2):478–485. doi: 10.1161/01.res.66.2.478. [DOI] [PubMed] [Google Scholar]
  17. Kashiwabara T., Nakajima S., Izawa T., Fukushima H., Nishikori K. Characteristics of KRN2391, a novel vasodilator, compared with those of cromakalim, pinacidil and nifedipine in rat aorta. Eur J Pharmacol. 1991 Apr 10;196(1):1–7. doi: 10.1016/0014-2999(91)90401-b. [DOI] [PubMed] [Google Scholar]
  18. Marshall R. J., Muir A. W., Winslow E. Effects of antiarrhythmic drugs on ventricular fibrillation thresholds of normal and ischaemic myocardium in the anaesthetized rat. Br J Pharmacol. 1983 Jan;78(1):165–171. doi: 10.1111/j.1476-5381.1983.tb09377.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Muto Y., Kudo S., Nozawa Y. Effects of local anesthetics on calmodulin-dependent guanylate cyclase in the plasma membrane of Tetrahymena pyriformis. Biochem Pharmacol. 1983 Dec 1;32(23):3559–3563. doi: 10.1016/0006-2952(83)90303-9. [DOI] [PubMed] [Google Scholar]
  20. Noma A. ATP-regulated K+ channels in cardiac muscle. Nature. 1983 Sep 8;305(5930):147–148. doi: 10.1038/305147a0. [DOI] [PubMed] [Google Scholar]
  21. Notsu T., Tanaka I., Takano M., Noma A. Blockade of the ATP-sensitive K+ channel by 5-hydroxydecanoate in guinea pig ventricular myocytes. J Pharmacol Exp Ther. 1992 Feb;260(2):702–708. [PubMed] [Google Scholar]
  22. Pang D. C., Sperelakis N. Uptake of calcium antagonistic drugs into muscles as related to their lipid solubilities. Biochem Pharmacol. 1984 Mar 1;33(5):821–826. doi: 10.1016/0006-2952(84)90468-4. [DOI] [PubMed] [Google Scholar]
  23. Pruett J. K., Walle T., Walle U. K. Propranolol effects on membrane repolarization time in isolated canine Purkinje fibers: threshold tissue content and the influence of exposure time. J Pharmacol Exp Ther. 1980 Nov;215(2):539–543. [PubMed] [Google Scholar]
  24. Sakuta H., Sekiguchi M., Okamoto K., Sakai Y. Inactivation of glibenclamide-sensitive K+ channels in Xenopus oocytes by various calmodulin antagonists. Eur J Pharmacol. 1992 Jul 1;226(3):199–207. doi: 10.1016/0922-4106(92)90062-z. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Singh B. N., Baky S., Nademanee K. Second-generation calcium antagonists: search for greater selectivity and versatility. Am J Cardiol. 1985 Jan 25;55(3):214B–221B. doi: 10.1016/0002-9149(85)90634-4. [DOI] [PubMed] [Google Scholar]
  27. Spruce A. E., Standen N. B., Stanfield P. R. Voltage-dependent ATP-sensitive potassium channels of skeletal muscle membrane. Nature. 1985 Aug 22;316(6030):736–738. doi: 10.1038/316736a0. [DOI] [PubMed] [Google Scholar]
  28. Sturgess N. C., Ashford M. L., Cook D. L., Hales C. N. The sulphonylurea receptor may be an ATP-sensitive potassium channel. Lancet. 1985 Aug 31;2(8453):474–475. doi: 10.1016/s0140-6736(85)90403-9. [DOI] [PubMed] [Google Scholar]
  29. Taggart P., Donaldson R., Abed J., Nashat F. Class III action of beta-blocking agents. Cardiovasc Res. 1984 Nov;18(11):683–689. doi: 10.1093/cvr/18.11.683. [DOI] [PubMed] [Google Scholar]
  30. Vaughan Williams E. M. A classification of antiarrhythmic actions reassessed after a decade of new drugs. J Clin Pharmacol. 1984 Apr;24(4):129–147. doi: 10.1002/j.1552-4604.1984.tb01822.x. [DOI] [PubMed] [Google Scholar]
  31. Volpi M., Sha'afi R. I., Epstein P. M., Andrenyak D. M., Feinstein M. B. Local anesthetics, mepacrine, and propranolol are antagonists of calmodulin. Proc Natl Acad Sci U S A. 1981 Feb;78(2):795–799. doi: 10.1073/pnas.78.2.795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Winslow E., Farmer S., Martorana M., Marshall R. J. The effects of bepridil compared with calcium antagonists on rat and rabbit aorta. Eur J Pharmacol. 1986 Nov 19;131(2-3):219–228. doi: 10.1016/0014-2999(86)90575-3. [DOI] [PubMed] [Google Scholar]
  33. Wolleben C. D., Sanguinetti M. C., Siegl P. K. Influence of ATP-sensitive potassium channel modulators on ischemia-induced fibrillation in isolated rat hearts. J Mol Cell Cardiol. 1989 Aug;21(8):783–788. doi: 10.1016/0022-2828(89)90717-7. [DOI] [PubMed] [Google Scholar]
  34. Woosley R. L. Antiarrhythmic drugs. Annu Rev Pharmacol Toxicol. 1991;31:427–455. doi: 10.1146/annurev.pa.31.040191.002235. [DOI] [PubMed] [Google Scholar]
  35. Zimmer M., Hofmann F. Differentiation of the drug-binding sites of calmodulin. Eur J Biochem. 1987 Apr 15;164(2):411–420. doi: 10.1111/j.1432-1033.1987.tb11073.x. [DOI] [PubMed] [Google Scholar]

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