Home LiteratureArticle Details
PMID: 2443683 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Cyclic guanosine 3',5'-monophosphate regulates the calcium current in single cells from frog ventricle.

The Journal of physiology ·Vol. 387 ·1987-06-00 ·Pages 453-72

Fischmeister R, Hartzell HC

Abstract

1. The effect of intracellular perfusion with cyclic AMP and cyclic GMP on Ca2+ current (ICa) was studied in single cells isolated from frog ventricle using the whole-cell patch-clamp technique and a perfused pipette. 2. Intracellular perfusion with cyclic GMP (0.1-20 microM) had no effect on the basal ICa. However, when ICa was increased by isoprenaline or by intracellular perfusion with cyclic AMP, perfusion with cyclic GMP (20 microM) reduced ICa by an average of 67%. The effect of cyclic GMP on ICa elevated by cyclic AMP was reversible. A half-maximal effect of cyclic GMP was observed at 0.6 microM. Cyclic GMP had no significant effect on the shape of the ICa current-voltage relationship. 3. The effect of cyclic GMP was specific to the 3',5' form; 2',3'-cyclic GMP had no effect. 4. The effect of cyclic GMP was apparently not mediated by stimulation of cyclic-GMP-dependent protein kinase because 8-bromo-cyclic GMP, a very potent activator of the protein kinase, was without effect. 5. Cyclic GMP had no effect on ICa elevated by the non-hydrolysable 8-bromo-cyclic AMP. The effect of cyclic GMP on cyclic-AMP-elevated ICa was partially blocked by the phosphodiesterase inhibitor, methylisobutylxanthine. Thus, it was hypothesized that the effect of cyclic GMP was mediated by hydrolysis of cyclic AMP as a result of a stimulation of a cyclic nucleotide phosphodiesterase by cyclic GMP. 6. The dose-response curve for cyclic AMP on ICa was well fitted by the Michaelis equation with a K50 (i.e. concentration of cyclic AMP at which response is 50% of the maximum) of 0.7 microM and a maximal 11-fold stimulation of ICa. Cyclic GMP shifted the curve one log unit to the right and decreased the maximal stimulation to 8.6-fold. Thus, the effect of cyclic GMP appeared uncompetitive. 7. The products of cyclic AMP and cyclic GMP hydrolysis, 5'-AMP and 5'-GMP, had no effect on ICa. Furthermore, strong buffering of intracellular pH did not reduce the effect of cyclic GMP. 8. It is proposed that cyclic-GMP-stimulation of a cyclic nucleotide phosphodiesterase may be one of several mechanisms by which acetylcholine regulates ICa.

MeSH Terms
1-Methyl-3-isobutylxanthine/pharmacology 8-Bromo Cyclic Adenosine Monophosphate/pharmacology Action Potentials/drug effects Animals Calcium/physiology Cyclic AMP/pharmacology Cyclic GMP/pharmacology Heart/physiology Hydrogen-Ion Concentration In Vitro Techniques Ion Channels/drug effects Rana esculenta Time Factors
Chemicals
Ion Channels 8-Bromo Cyclic Adenosine Monophosphate Cyclic AMP Cyclic GMP Calcium 1-Methyl-3-isobutylxanthine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Fischmeister R
Laboratoire de Physiologie Cellulaire Cardiaque, INSERM Unité 241, Université de Paris-Sud, Orsay, France.
Hartzell H C
References (56)
56 references, click to expand
  1. The effect of intracellular cyclic nucleotides and calcium on the action potential and acetylcholine response of isolated cardiac cells.
    Pflugers Arch. 1982 Feb;392(4):307-14 PMID: 6280126
  2. Injection of guanosine 5'-cyclic monophosphate into heart cells blocks calcium slow channels.
    Am J Physiol. 1985 May;248(5 Pt 2):H745-9 PMID: 2581461
  3. Cyclic GMP directly regulates a cation conductance in membranes of bovine rods by a cooperative mechanism.
    J Biol Chem. 1985 Jun 10;260(11):6788-800 PMID: 2581960
  4. Membrane currents and their modification by acetylcholine in isolated single atrial cells of the guinea-pig.
    J Physiol. 1985 Feb;359:485-501 PMID: 2582116
  5. The parasympathetic neuroeffector junction of the heart.
    Pharmacol Rev. 1985 Mar;37(1):1-24 PMID: 2408285
  6. Time course of the increase in the myocardial slow inward current after a photochemically generated concentration jump of intracellular cAMP.
    Proc Natl Acad Sci U S A. 1983 Apr;80(8):2395-9 PMID: 6300914
  7. Calcium channels in excitable cell membranes.
    Annu Rev Physiol. 1983;45:341-58 PMID: 6303205
  8. Magnitude of increase in retinal cGMP metabolic flux determined by 18O incorporation into nucleotide alpha-phosphoryls corresponds with intensity of photic stimulation.
    J Biol Chem. 1983 Aug 10;258(15):9213-9 PMID: 6307996
  9. Beta-adrenergic modulation of calcium channels in frog ventricular heart cells.
    Nature. 1984 Jan 26-Feb 1;307(5949):371-5 PMID: 6320002
  10. Mode of regulation of the ACh-sensitive K-channel by the muscarinic receptor in rabbit atrial cells.
    Pflugers Arch. 1984 Apr;400(4):424-31 PMID: 6087268
  11. Induction by cyclic GMP of cationic conductance in plasma membrane of retinal rod outer segment.
    Nature. 1985 Jan 24-30;313(6000):310-3 PMID: 2578616
  12. Intracellular injection of cyclic GMP depresses cardiac slow action potentials.
    J Cyclic Nucleotide Protein Phosphor Res. 1985;10(1):83-95 PMID: 2984266
  13. A new generation of phosphodiesterase inhibitors: multiple molecular forms of phosphodiesterase and the potential for drug selectivity.
    J Med Chem. 1985 May;28(5):537-45 PMID: 2985781
  14. Elevation of guanosine 3',5'-cyclic phosphate in rat heart after perfusion with acetylcholine.
    Proc Natl Acad Sci U S A. 1970 Jun;66(2):398-403 PMID: 5271171
  15. Stimulation of adenosine 3',5'-monophosphate hydrolysis by guanosine 3',5'-monophosphate.
    J Biol Chem. 1971 Jun 25;246(12):3841-6 PMID: 4327188
  16. Cyclic nucleotide-dependent protein kinases. X. An assay method for the measurement of quanosine 3',5'-monophosphate in various biological materials and a study of agents regulating its levels in heart and brain.
    J Biol Chem. 1972 Jan 10;247(1):16-22 PMID: 4336039
  17. Biologic regulation through opposing influences of cyclic GMP and cyclic AMP: the Yin Yang hypothesis.
    Adv Cyclic Nucleotide Res. 1975;5:307-30 PMID: 165672
  18. Interaction between cyclic adenosine monophosphate and cyclic gunaosine monophosphate in guinea pig ventricular myocardium.
    Circ Res. 1975 Sep;37(3):309-17 PMID: 168986
  19. On the mechanism of the negative inotropic effect of acetylcholine.
    Pflugers Arch. 1976 Feb 24;361(3):207-13 PMID: 943764
  20. Effects of derivatives of cyclic amp and cyclic gmp on contraction force of cat papillary muscles.
    Eur J Pharmacol. 1976 Mar;36(1):247-51 PMID: 177300
  21. Oppositional effects of acetylcholine and isoproterenol on isometric tension and cyclic nucleotide concentrations in rabbit atria.
    J Cyclic Nucleotide Res. 1975;1(5):339-47 PMID: 178695
  22. Effect of acetylcholine on glycogen phosphorylase activity and cyclic nucleotide content in isolated perfused rat hearts.
    J Cyclic Nucleotide Res. 1976;2(3):171-8 PMID: 180066
  23. Involvement of cyclic nucleotides in the beating response of rat heart cells in culture.
    J Mol Cell Cardiol. 1976 Jun;8(6):481-8 PMID: 7680
  24. Negative inotropic effect of cyclic GMP in cardiac fiber fragments.
    Pflugers Arch. 1976 Nov 5;366(2-3):293-5 PMID: 186756
  25. Does cyclic GMP mediate the negative inotropic effect of acetylcholine in the heart?
    Nature. 1977 May 5;267(5606):72-4 PMID: 193045
  26. Cyclic GMP metabolism and involvement in biological regulation.
    Annu Rev Biochem. 1977;46:823-96 PMID: 20041
  27. Effects of sodium nitroprusside, nitroglycerin, and sodium azide on levels of cyclic nucleotides and mechanical activity of various tissues.
    J Cyclic Nucleotide Res. 1977 Aug;3(4):239-47 PMID: 199626
  28. Cyclic AMP and contractile activity in heart.
    Adv Cyclic Nucleotide Res. 1977;8:363-420 PMID: 21550
  29. Are increases in cyclic GMP levels responsible for the negative inotropic effects of acetylcholine in the heart?
    Biochem Biophys Res Commun. 1977 Dec 7;79(3):912-8 PMID: 202278
  30. Dissociation of cyclic GMP from the negative inotropic action of carbachol in guinea pig atria.
    J Cyclic Nucleotide Res. 1977 Dec;3(6):407-13 PMID: 203613
  31. 8-bromo-guanosine-3',5' -monophosphate mimics the effect of acetylcholine on slow response action potential and contractile force in mammalian atrial myocardium.
    J Mol Cell Cardiol. 1978 Jun;10(6):573-86 PMID: 211240
  32. Properties of two inward membrane currents in the heart.
    Annu Rev Physiol. 1979;41:413-24 PMID: 373598
  33. Characterization of a novel cGMP binding protein from rat lung.
    J Biol Chem. 1980 Jan 25;255(2):620-6 PMID: 6153179
  34. Influence of isoproterenol and methylisobutylxanthine on the contractile and cyclic nucleotide effects of methacholine in isolated rat atria.
    J Pharmacol Exp Ther. 1980 Feb;212(2):325-32 PMID: 6153218
  35. The questionable role of cyclic guanosine 3':5'-monophosphate in heart.
    Biochem Pharmacol. 1979 Dec 1;28(23):3351-60 PMID: 43730
  36. Failure of dibutyryl and 8-bromo-cyclic GMP to mimic the antagonistic action of carbachol on the positive inotropic effects of sympathomimetic amines in the canine isolated ventricular myocardium.
    Jpn J Pharmacol. 1979 Jun;29(3):423-33 PMID: 231701
  37. Differential responses to carbachol, sodium nitroprusside and 8-bromo-guanosine 3',5'-monophosphate of canine atrial and ventricular muscle.
    Br J Pharmacol. 1981 Jun;73(2):393-9 PMID: 6263387
  38. Specificity of cyclic GMP activation of a multi-substrate cyclic nucleotide phosphodiesterase from rat liver.
    Eur J Biochem. 1981 Apr;115(3):503-10 PMID: 6263632
  39. Regulation of cardiac cyclic GMP-dependent protein kinase.
    Biochim Biophys Acta. 1981 Aug 17;676(2):230-44 PMID: 6266503
  40. Inotropic responses of the frog ventricle to dibutyryl cyclic AMP and 8-bromo cyclic GMP and related changes in endogenous cyclic nucleotide levels.
    Biochem Pharmacol. 1981 Jun 15;30(12):1475-81 PMID: 6268101
  41. The effect of acetylcholine, ischemia, and anoxia on rat heart purine cyclic nucleotides and contractility.
    Circ Res. 1981 Oct;49(4):912-22 PMID: 6268333
  42. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
    Pflugers Arch. 1981 Aug;391(2):85-100 PMID: 6270629
  43. Cyclic GMP-dependent phosphorylation of an endogenous protein from rat heart.
    Biochem Biophys Res Commun. 1981 Aug 31;101(4):1274-80 PMID: 6272778
  44. Are acetylcholine-induced increases in 42K efflux mediated by intracellular cyclic GMP in turtle cardiac pace-maker tissue?
    J Physiol. 1981 May;314:47-64 PMID: 6273536
  45. Evidence that cyclic GMP may regulate cyclic AMP metabolism in the isolated frog ventricle.
    J Mol Cell Cardiol. 1981 Nov;13(11):963-79 PMID: 6275088
  46. Purification and characterization of a cyclic GMP-stimulated cyclic nucleotide phosphodiesterase from bovine tissues.
    J Biol Chem. 1982 Feb 25;257(4):1973-9 PMID: 6276403
  47. Attenuation of muscarinic cholinergic inhibition by islet-activating protein in the heart.
    Am J Physiol. 1985 Aug;249(2 Pt 2):H309-20 PMID: 2992293
  48. GTP-binding proteins couple cardiac muscarinic receptors to a K channel.
    Nature. 1985 Oct 10-16;317(6037):536-8 PMID: 2413367
  49. Cardiac calcium channels and their control by neurotransmitters and drugs.
    J Am Coll Cardiol. 1985 Dec;6(6):1409-16 PMID: 2415563
  50. On the mechanism of beta-adrenergic regulation of the Ca channel in the guinea-pig heart.
    Pflugers Arch. 1985 Oct;405(3):285-93 PMID: 2415919
  51. A novel cyclic GMP-lowering agent, LY83583, blocks carbachol-induced cyclic GMP elevation in rabbit atrial strips without blocking the negative inotropic effects of carbachol.
    Can J Physiol Pharmacol. 1985 Aug;63(8):908-11 PMID: 3000562
  52. Studies of cGMP analog specificity and function of the two intrasubunit binding sites of cGMP-dependent protein kinase.
    J Biol Chem. 1986 Jan 25;261(3):1208-14 PMID: 3003061
  53. Multiple molecular forms of cyclic nucleotide phosphodiesterase in cardiac and smooth muscle and in platelets. Isolation, characterization, and effects of various reference phosphodiesterase inhibitors and cardiotonic agents.
    Biochem Pharmacol. 1986 Mar 1;35(5):787-800 PMID: 3006691
  54. Opposite effects of cyclic GMP and cyclic AMP on Ca2+ current in single heart cells.
    Nature. 1986 Sep 18-24;323(6085):273-5 PMID: 2429189
  55. Mechanism of action of acetylcholine on calcium current in single cells from frog ventricle.
    J Physiol. 1986 Jul;376:183-202 PMID: 2432231
  56. Calcium channel modulation by neurotransmitters, enzymes and drugs.
    Nature. 1983 Feb 17-23;301(5901):569-74 PMID: 6131381
Article Info
Journal
The Journal of physiology
Abbr.
J Physiol
ISSN
0022-3751
DOI
10.1113/jphysiol.1987.sp016584
Published
1987-06-00
Pages
453-72
Language
English
Region
England
NLM ID
0266262
PMCID
PMC1192515
Subset
IM
Grants
NHLBI NIH HHS · HL-21195 · United States
NHLBI NIH HHS · HL-27385 · United States
External Links
PubMed source DOI: 10.1113/jphysiol.1987.sp016584 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2