Skip to main content
NCBI home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1991 Jun;437:239–256. doi: 10.1113/jphysiol.1991.sp018593

On the mechanism of nucleotide diphosphate activation of the ATP-sensitive K+ channel in ventricular cell of guinea-pig.

R T Tung 1, Y Kurachi 1
PMCID: PMC1180045  PMID: 1890633

Abstract

1. Effects of intracellular nucleotide diphosphates (NDPs) on the ATP-sensitive K+ channel (K+ATP channel) were examined in ventricular cells of guinea-pig heart, using the inside-out patch clamp technique. On formation of inside-out patches in the ATP-free internal solution, the K+ATP channel appeared and then ran down spontaneously. This run-down of the K+ATP channel activity was probably due to dephosphorylation. 2. Millimolar concentrations of various NDPs, e.g. UDP (uridine diphosphate), IDP (inosine diphosphate), CDP (cytidine diphosphate) and GDP (guanosine diphosphate), applied to the internal side of the patch membrane, induced openings of the K+ATP channel after run-down, i.e. in the dephosphorylated state. ADP opened the channel weakly at low concentrations (100 microM) but inhibited it at higher concentrations (1-10 mM). 3. NDP-induced openings of the channel were Mg2+ dependent and inhibited by ATP (100 microM) and glibenclamide (1 microM). None of nucleosides, nucleotide monophosphates nor nucleotide triphosphates induced openings of the channel. Thus, the K+ATP channel may have a Mg(2+)-dependent NDP-binding site, which induces openings of the dephosphorylated channel in ATP-free solution, in addition to the Mg(2+)-independent ATP-binding inactivation site and phosphorylation site. 4. In inside-out patches, pinacidil (a K+ATP channel opener) activated the K+ATP channel in the phosphorylated state but not in the dephosphorylated state. In the presence of NDPs (UDP, IDP, CDP, GDP), however, pinacidil (30 microM) enhanced openings of the dephosphorylated K+ATP channel prominently. 5. From the above results, we concluded that NDP-binding to the specific site has similar effects to channel phosphorylation, i.e. it keeps the K+ATP channel in an operative state in ATP-free solution and enhances the pinacidil-induced channel openings.

Full text

PDF
239

Selected References

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

  1. Allen D. G., Morris P. G., Orchard C. H., Pirolo J. S. A nuclear magnetic resonance study of metabolism in the ferret heart during hypoxia and inhibition of glycolysis. J Physiol. 1985 Apr;361:185–204. doi: 10.1113/jphysiol.1985.sp015640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. 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]
  4. Davies N. W. Modulation of ATP-sensitive K+ channels in skeletal muscle by intracellular protons. Nature. 1990 Jan 25;343(6256):375–377. doi: 10.1038/343375a0. [DOI] [PubMed] [Google Scholar]
  5. Dunne M. J., Petersen O. H. GTP and GDP activation of K+ channels that can be inhibited by ATP. Pflugers Arch. 1986 Nov;407(5):564–565. doi: 10.1007/BF00657518. [DOI] [PubMed] [Google Scholar]
  6. Fabiato A., Fabiato F. Calculator programs for computing the composition of the solutions containing multiple metals and ligands used for experiments in skinned muscle cells. J Physiol (Paris) 1979;75(5):463–505. [PubMed] [Google Scholar]
  7. 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]
  8. Findlay I. ATP4- and ATP.Mg inhibit the ATP-sensitive K+ channel of rat ventricular myocytes. Pflugers Arch. 1988 Jul;412(1-2):37–41. doi: 10.1007/BF00583729. [DOI] [PubMed] [Google Scholar]
  9. Findlay I., Deroubaix E., Guiraudou P., Coraboeuf E. Effects of activation of ATP-sensitive K+ channels in mammalian ventricular myocytes. Am J Physiol. 1989 Nov;257(5 Pt 2):H1551–H1559. doi: 10.1152/ajpheart.1989.257.5.H1551. [DOI] [PubMed] [Google Scholar]
  10. Findlay I. Effects of ADP upon the ATP-sensitive K+ channel in rat ventricular myocytes. J Membr Biol. 1988;101(1):83–92. doi: 10.1007/BF01872823. [DOI] [PubMed] [Google Scholar]
  11. Findlay I. The effects of magnesium upon adenosine triphosphate-sensitive potassium channels in a rat insulin-secreting cell line. J Physiol. 1987 Oct;391:611–629. doi: 10.1113/jphysiol.1987.sp016759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  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. Horie M., Irisawa H., Noma A. Voltage-dependent magnesium block of adenosine-triphosphate-sensitive potassium channel in guinea-pig ventricular cells. J Physiol. 1987 Jun;387:251–272. doi: 10.1113/jphysiol.1987.sp016572. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Kakei M., Kelly R. P., Ashcroft S. J., Ashcroft F. M. The ATP-sensitivity of K+ channels in rat pancreatic B-cells is modulated by ADP. FEBS Lett. 1986 Nov 10;208(1):63–66. doi: 10.1016/0014-5793(86)81533-2. [DOI] [PubMed] [Google Scholar]
  18. Kakei M., Noma A. Adenosine-5'-triphosphate-sensitive single potassium channel in the atrioventricular node cell of the rabbit heart. J Physiol. 1984 Jul;352:265–284. doi: 10.1113/jphysiol.1984.sp015290. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kakei M., Noma A., Shibasaki T. Properties of adenosine-triphosphate-regulated potassium channels in guinea-pig ventricular cells. J Physiol. 1985 Jun;363:441–462. doi: 10.1113/jphysiol.1985.sp015721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kurachi Y. The effects of intracellular protons on the electrical activity of single ventricular cells. Pflugers Arch. 1982 Sep;394(3):264–270. doi: 10.1007/BF00589102. [DOI] [PubMed] [Google Scholar]
  21. Kurachi Y. Voltage-dependent activation of the inward-rectifier potassium channel in the ventricular cell membrane of guinea-pig heart. J Physiol. 1985 Sep;366:365–385. doi: 10.1113/jphysiol.1985.sp015803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lederer W. J., Nichols C. G. Nucleotide modulation of the activity of rat heart ATP-sensitive K+ channels in isolated membrane patches. J Physiol. 1989 Dec;419:193–211. doi: 10.1113/jphysiol.1989.sp017869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Misler S., Falke L. C., Gillis K., McDaniel M. L. A metabolite-regulated potassium channel in rat pancreatic B cells. Proc Natl Acad Sci U S A. 1986 Sep;83(18):7119–7123. doi: 10.1073/pnas.83.18.7119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Nelson M. T., Huang Y., Brayden J. E., Hescheler J., Standen N. B. Arterial dilations in response to calcitonin gene-related peptide involve activation of K+ channels. Nature. 1990 Apr 19;344(6268):770–773. doi: 10.1038/344770a0. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Ohno-Shosaku T., Zünkler B. J., Trube G. Dual effects of ATP on K+ currents of mouse pancreatic beta-cells. Pflugers Arch. 1987 Feb;408(2):133–138. doi: 10.1007/BF00581342. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Spruce A. E., Standen N. B., Stanfield P. R. Studies of the unitary properties of adenosine-5'-triphosphate-regulated potassium channels of frog skeletal muscle. J Physiol. 1987 Jan;382:213–236. doi: 10.1113/jphysiol.1987.sp016364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. 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]
  31. Takano M., Qin D. Y., Noma A. ATP-dependent decay and recovery of K+ channels in guinea pig cardiac myocytes. Am J Physiol. 1990 Jan;258(1 Pt 2):H45–H50. doi: 10.1152/ajpheart.1990.258.1.H45. [DOI] [PubMed] [Google Scholar]
  32. 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]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES