Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1991 Jul;103(3):1641–1648. doi: 10.1111/j.1476-5381.1991.tb09841.x

Action of nicorandil on ATP-sensitive K+ channel in guinea-pig ventricular myocytes.

K Nakayama 1, Z Fan 1, F Marumo 1, T Sawanobori 1, M Hiraoka 1
PMCID: PMC1907802  PMID: 1834294

Abstract

1. Patch-clamp techniques were used to study the effects of nicorandil (2-nicotinamiodethyl nitrate) on the adenosine 5'-triphosphate (ATP)-sensitive K+ channel current (IK.ATP) in guinea-pig ventricular myocytes. 2. Nicorandil activated the time-independent outward current. This effect was dependent on intracellular ATP concentration ([ATP]i) showing a larger effect at 2 mM than at 10 mM [ATP]i. The nicorandil-induced outward current was inhibited by application of 0.3 microM glibenclamide. 3. In the inside-out patch configuration, 0.3-1.0 mM nicorandil increased the open-stage probability of IK.ATP without a change in its conductance value (about 90pS). This effect was inhibited by glibenclamide. Analysis of the open and closed time distributions showed that nicorandil had no effect on open and closed distributions shorter than 5 ms. On the other hand, nicorandil increased the life time of bursts and decreased the interburst intervals. 4 The inward rectifier K+ channel current was not influenced by internal application of nicorandil. 5 Therefore, we conclude that IK.ATP is the only K+ current activated by nicorandil, and the main effect of nicorandil is on the kinetics of the IK.ATP bursting behaviour. These actions are similar to that of pinacidil on this preparation.

Full text

PDF
1644

Selected References

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

  1. Arena J. P., Kass R. S. Activation of ATP-sensitive K channels in heart cells by pinacidil: dependence on ATP. Am J Physiol. 1989 Dec;257(6 Pt 2):H2092–H2096. doi: 10.1152/ajpheart.1989.257.6.H2092. [DOI] [PubMed] [Google Scholar]
  2. Arena J. P., Kass R. S. Enhancement of potassium-sensitive current in heart cells by pinacidil. Evidence for modulation of the ATP-sensitive potassium channel. Circ Res. 1989 Aug;65(2):436–445. doi: 10.1161/01.res.65.2.436. [DOI] [PubMed] [Google Scholar]
  3. Ashcroft F. M. Adenosine 5'-triphosphate-sensitive potassium channels. Annu Rev Neurosci. 1988;11:97–118. doi: 10.1146/annurev.ne.11.030188.000525. [DOI] [PubMed] [Google Scholar]
  4. Cook N. S. The pharmacology of potassium channels and their therapeutic potential. Trends Pharmacol Sci. 1988 Jan;9(1):21–28. doi: 10.1016/0165-6147(88)90238-6. [DOI] [PubMed] [Google Scholar]
  5. Dunne M. J. Effects of pinacidil, RP 49356 and nicorandil on ATP-sensitive potassium channels in insulin-secreting cells. Br J Pharmacol. 1990 Mar;99(3):487–492. doi: 10.1111/j.1476-5381.1990.tb12955.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Escande D., Thuringer D., Le Guern S., Courteix J., Laville M., Cavero I. Potassium channel openers act through an activation of ATP-sensitive K+ channels in guinea-pig cardiac myocytes. Pflugers Arch. 1989 Sep;414(6):669–675. doi: 10.1007/BF00582134. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Fan Z., Nakayama K., Hiraoka M. Pinacidil activates the ATP-sensitive K+ channel in inside-out and cell-attached patch membranes of guinea-pig ventricular myocytes. Pflugers Arch. 1990 Jan;415(4):387–394. doi: 10.1007/BF00373613. [DOI] [PubMed] [Google Scholar]
  9. Fosset M., De Weille J. R., Green R. D., Schmid-Antomarchi H., Lazdunski M. Antidiabetic sulfonylureas control action potential properties in heart cells via high affinity receptors that are linked to ATP-dependent K+ channels. J Biol Chem. 1988 Jun 15;263(17):7933–7936. [PubMed] [Google Scholar]
  10. Gelband C. H., Lodge N. J., Van Breemen C. A Ca2+-activated K+ channel from rabbit aorta: modulation by cromakalim. Eur J Pharmacol. 1989 Aug 22;167(2):201–210. doi: 10.1016/0014-2999(89)90580-3. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Hamilton T. C., Weir S. W., Weston A. H. Comparison of the effects of BRL 34915 and verapamil on electrical and mechanical activity in rat portal vein. Br J Pharmacol. 1986 May;88(1):103–111. doi: 10.1111/j.1476-5381.1986.tb09476.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Hiraoka M., Fan Z. Activation of ATP-sensitive outward K+ current by nicorandil (2-nicotinamidoethyl nitrate) in isolated ventricular myocytes. J Pharmacol Exp Ther. 1989 Jul;250(1):278–285. [PubMed] [Google Scholar]
  15. Imanishi S., Arita M., Kiyosue T., Aomine M. Effects of SG-75 (nicorandil) on electrical activity of canine cardiac Purkinje fibers: possible increase in potassium conductance. J Pharmacol Exp Ther. 1983 Apr;225(1):198–205. [PubMed] [Google Scholar]
  16. Inoue I., Nakaya Y., Nakaya S., Mori H. Extracellular Ca2+-activated K channel in coronary artery smooth muscle cells and its role in vasodilation. FEBS Lett. 1989 Sep 25;255(2):281–284. doi: 10.1016/0014-5793(89)81106-8. [DOI] [PubMed] [Google Scholar]
  17. Kajioka S., Oike M., Kitamura K. Nicorandil opens a calcium-dependent potassium channel in smooth muscle cells of the rat portal vein. J Pharmacol Exp Ther. 1990 Sep;254(3):905–913. [PubMed] [Google Scholar]
  18. Kakei M., Yoshinaga M., Saito K., Tanaka H. The potassium current activated by 2-nicotinamidoethyl nitrate (nicorandil) in single ventricular cells of guinea pigs. Proc R Soc Lond B Biol Sci. 1986 Dec 22;229(1256):331–343. doi: 10.1098/rspb.1986.0089. [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. Lindau M., Neher E. Patch-clamp techniques for time-resolved capacitance measurements in single cells. Pflugers Arch. 1988 Feb;411(2):137–146. doi: 10.1007/BF00582306. [DOI] [PubMed] [Google Scholar]
  21. Nakayama K., Fan Z., Marumo F., Hiraoka M. Interrelation between pinacidil and intracellular ATP concentrations on activation of the ATP-sensitive K+ current in guinea pig ventricular myocytes. Circ Res. 1990 Nov;67(5):1124–1133. doi: 10.1161/01.res.67.5.1124. [DOI] [PubMed] [Google Scholar]
  22. Osterrieder W. Modification of K+ conductance of heart cell membrane by BRL 34915. Naunyn Schmiedebergs Arch Pharmacol. 1988 Jan;337(1):93–97. doi: 10.1007/BF00169483. [DOI] [PubMed] [Google Scholar]
  23. Sakmann B., Trube G. Conductance properties of single inwardly rectifying potassium channels in ventricular cells from guinea-pig heart. J Physiol. 1984 Feb;347:641–657. doi: 10.1113/jphysiol.1984.sp015088. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sanguinetti M. C., Scott A. L., Zingaro G. J., Siegl P. K. BRL 34915 (cromakalim) activates ATP-sensitive K+ current in cardiac muscle. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8360–8364. doi: 10.1073/pnas.85.21.8360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Smallwood J. K., Steinberg M. I. Cardiac electrophysiological effects of pinacidil and related pyridylcyanoguanidines: relationship to antihypertensive activity. J Cardiovasc Pharmacol. 1988 Jul;12(1):102–109. doi: 10.1097/00005344-198807000-00014. [DOI] [PubMed] [Google Scholar]
  26. Standen N. B., Quayle J. M., Davies N. W., Brayden J. E., Huang Y., Nelson M. T. Hyperpolarizing vasodilators activate ATP-sensitive K+ channels in arterial smooth muscle. Science. 1989 Jul 14;245(4914):177–180. doi: 10.1126/science.2501869. [DOI] [PubMed] [Google Scholar]
  27. Takano M., Noma A. Selective modulation of the ATP-sensitive K+ channel by nicorandil in guinea-pig cardiac cell membrane. Naunyn Schmiedebergs Arch Pharmacol. 1990 Nov;342(5):592–597. doi: 10.1007/BF00169050. [DOI] [PubMed] [Google Scholar]
  28. Trube G., Hescheler J. Inward-rectifying channels in isolated patches of the heart cell membrane: ATP-dependence and comparison with cell-attached patches. Pflugers Arch. 1984 Jun;401(2):178–184. doi: 10.1007/BF00583879. [DOI] [PubMed] [Google Scholar]
  29. Yanagisawa T., Taira N. Effect of 2-nicotinamidethyl nitrate (SG-75) on the membrane potential of left atrial muscle fibres of the dog. Increase in potassium conductance. Naunyn Schmiedebergs Arch Pharmacol. 1980 May;312(1):69–76. doi: 10.1007/BF00502577. [DOI] [PubMed] [Google Scholar]
  30. Yellen G. Ionic permeation and blockade in Ca2+-activated K+ channels of bovine chromaffin cells. J Gen Physiol. 1984 Aug;84(2):157–186. doi: 10.1085/jgp.84.2.157. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES