Home LiteratureArticle Details
PMID: 9417139 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Nitric oxide signaling mediates stimulation of L-type Ca2+ current elicited by withdrawal of acetylcholine in cat atrial myocytes.

The Journal of general physiology ·Vol. 111 ·No. 1 ·1998-01-00 ·Pages 113-25

Wang YG, Rechenmacher CE, Lipsius SL

Abstract

A perforated-patch whole-cell recording method was used to determine whether nitric oxide signaling participates in acetylcholine (ACh)-induced regulation of basal L-type Ca2+ current (ICa,L) in cat atrial myocytes. Exposure to 1 microM ACh for 2 min inhibited basal ICa,L (-21 +/- 3%), and withdrawal of ACh elicited rebound stimulation of ICa,L above control (80 +/- 13%) (n = 23). Stimulation of ICa,L elicited by withdrawal of ACh (but not ACh-induced inhibition of ICa,L) was blocked by either 50 microM hemoglobin; 30 microM ODQ or 10 microM methylene blue, inhibitors of soluble guanylate cyclase; 10 microM W-7, a calmodulin inhibitor; or 10 microM L-NIO, an inhibitor of constitutive NO synthase (NOS). In cells incubated in 5 mM L-arginine, ACh-induced rebound stimulation of ICa,L was enhanced compared with control responses. Histochemical assay (NADPH diaphorase) indicated that atrial myocytes express constitutive NOS. NO-donor, spermine/NO (SP/NO), >1 microM stimulated basal ICa,L. SP/NO-induced stimulation of ICa,L was inhibited by 50 microM hemoglobin, 30 microM ODQ, or 5 microM H-89, an inhibitor of PKA, and was unchanged by 50 microM MnTBAP, a peroxynitrite scavenger. When ICa,L was prestimulated by 10 microM milrinone, an inhibitor of cGMP-inhibited phosphodiesterase (type III) activity, SP/NO failed to further increase ICa,L. In cells incubated in pertussis toxin (3.4 microg/ml for 6 h; 36 degrees C), ACh failed to affect ICa,L, but 100 microM SP/NO or 10 microM milrinone still increased basal ICa,L. These results indicate that in cat atrial myocytes NO signaling mediates stimulation of ICa,L elicited by withdrawal of ACh but not ACh-induced inhibition of basal ICa,L. NO activates cGMP-induced inhibition of phosphodiesterase (type III) activity. Upon withdrawal of ACh, this mechanism allows cAMP to recover to levels above control, thereby stimulating ICa,L. Pertussis toxin-sensitive G-proteins couple M2 muscarinic receptors to NO signaling. NO-mediated stimulation of ICa, L elicited by withdrawal of ACh may be an important mechanism that rapidly restores cardiac pacemaker and contractile functions after cholinergic suppression of atrial activity.

MeSH Terms
Acetylcholine/pharmacology Animals Arginine/pharmacology Calcium Channels/physiology Calmodulin/metabolism Cats Cyclic AMP/agonists,metabolism Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors,metabolism Cyclic GMP/metabolism Electrophysiology Enzyme Activation Enzyme Inhibitors/pharmacology Female Guanylate Cyclase/metabolism Heart Atria/cytology Hemoglobins/pharmacology Histocytochemistry Isoquinolines/pharmacology Male Muscle Fibers, Skeletal/chemistry,enzymology Myocardium/cytology Nitric Oxide/metabolism Pertussis Toxin Phosphodiesterase Inhibitors/pharmacology Phosphoric Diester Hydrolases/metabolism Signal Transduction/drug effects Spermine/pharmacology Sulfonamides Virulence Factors, Bordetella/pharmacology
Chemicals
Calcium Channels Calmodulin Enzyme Inhibitors Hemoglobins Isoquinolines Phosphodiesterase Inhibitors Sulfonamides Virulence Factors, Bordetella Spermine Nitric Oxide Arginine Cyclic AMP Pertussis Toxin Cyclic AMP-Dependent Protein Kinases Phosphoric Diester Hydrolases Guanylate Cyclase Cyclic GMP N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide Acetylcholine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Wang Y G
Department of Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois 60153, USA.
Rechenmacher C E
Lipsius S L
References (45)
45 references, click to expand
  1. Biochemistry of nitric oxide and its redox-activated forms.
    Science. 1992 Dec 18;258(5090):1898-902 PMID: 1281928
  2. Nitric oxide regulates the calcium current in isolated human atrial myocytes.
    J Clin Invest. 1995 Feb;95(2):794-802 PMID: 7860763
  3. Nitric oxide and cardiac function.
    Circ Res. 1996 Sep;79(3):363-80 PMID: 8781470
  4. Redox modulation of L-type calcium channels in ferret ventricular myocytes. Dual mechanism regulation by nitric oxide and S-nitrosothiols.
    J Gen Physiol. 1996 Oct;108(4):277-93 PMID: 8894977
  5. Regulation by acetylcholine of Ca2+ current in rabbit atrioventricular node cells.
    Am J Physiol. 1996 Dec;271(6 Pt 2):H2274-82 PMID: 8997283
  6. Rebound stimulation of the cAMP-regulated Cl- current by acetylcholine in guinea-pig ventricular myocytes.
    J Physiol. 1997 Feb 15;499 ( Pt 1):105-20 PMID: 9061643
  7. Withdrawal of acetylcholine elicits Ca2+-induced delayed afterdepolarizations in cat atrial myocytes.
    Circulation. 1997 Aug 19;96(4):1275-81 PMID: 9286959
  8. The kinetics and equilibria of the reactions of nitric oxide with sheep haemoglobin.
    J Physiol. 1957 May 23;136(3):507-24 PMID: 13429517
  9. Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside and nitric oxide: evidence for the involvement of S-nitrosothiols as active intermediates.
    J Pharmacol Exp Ther. 1981 Sep;218(3):739-49 PMID: 6115052
  10. 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
  11. N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, a calmodulin antagonist, inhibits cell proliferation.
    Proc Natl Acad Sci U S A. 1981 Jul;78(7):4354-7 PMID: 6945588
  12. Transient increase in the slow inward current following acetylcholine removal in catecholamine-treated guinea-pig Purkinje fibers.
    Jpn J Physiol. 1984;34(4):775-9 PMID: 6094896
  13. Acetylcholine elicits a rebound stimulation of Ca2+ current mediated by pertussis toxin-sensitive G protein and cAMP-dependent protein kinase A in atrial myocytes.
    Circ Res. 1995 Apr;76(4):634-44 PMID: 7895337
  14. NO+, NO, and NO- donation by S-nitrosothiols: implications for regulation of physiological functions by S-nitrosylation and acceleration of disulfide formation.
    Arch Biochem Biophys. 1995 Apr 20;318(2):279-85 PMID: 7733655
  15. Nitric oxide-dependent parasympathetic signaling is due to activation of constitutive endothelial (type III) nitric oxide synthase in cardiac myocytes.
    J Biol Chem. 1995 Jun 16;270(24):14582-6 PMID: 7540173
  16. Potent and selective inhibition of nitric oxide-sensitive guanylyl cyclase by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one.
    Mol Pharmacol. 1995 Aug;48(2):184-8 PMID: 7544433
  17. A metalloporphyrin superoxide dismutase mimetic protects against paraquat-induced endothelial cell injury, in vitro.
    J Pharmacol Exp Ther. 1995 Dec;275(3):1227-32 PMID: 8531085
  18. A cellular mechanism for nitric oxide-mediated cholinergic control of mammalian heart rate.
    J Gen Physiol. 1995 Jul;106(1):45-65 PMID: 7494138
  19. In situ identification of messenger RNA of endothelial type nitric oxide synthase in rat cardiac myocytes.
    Biochem Biophys Res Commun. 1996 Jan 17;218(2):601-5 PMID: 8561802
  20. Novel guanylyl cyclase inhibitor potently inhibits cyclic GMP accumulation in endothelial cells and relaxation of bovine pulmonary artery.
    J Pharmacol Exp Ther. 1996 Apr;277(1):48-53 PMID: 8613957
  21. Evaluation of the relative contribution of nitric oxide and peroxynitrite to the suppression of mitochondrial respiration in immunostimulated macrophages using a manganese mesoporphyrin superoxide dismutase mimetic and peroxynitrite scavenger.
    FEBS Lett. 1996 Feb 26;381(1-2):82-6 PMID: 8641445
  22. Genetic expression of endothelial nitric oxide synthase in human atrial myocardium.
    Mayo Clin Proc. 1996 Apr;71(4):346-50 PMID: 8637256
  23. Nitric oxide synthase activity in guinea pig ventricular myocytes is not involved in muscarinic inhibition of cAMP-regulated ion channels.
    Circ Res. 1996 May;78(5):925-35 PMID: 8620613
  24. A cellular mechanism contributing to postvagal tachycardia studied in isolated pacemaker cells from cat right atrium.
    Circ Res. 1996 Jul;79(1):109-14 PMID: 8925558
  25. Isolation and characterization of bovine cardiac muscle cGMP-inhibited phosphodiesterase: a receptor for new cardiotonic drugs.
    Mol Pharmacol. 1986 May;29(5):506-14 PMID: 3010079
  26. Enhanced cAMP accumulation after termination of cholinergic action in the heart.
    FASEB J. 1987 Aug;1(2):119-24 PMID: 2440752
  27. Muscarinic activation of ionic currents measured by a new whole-cell recording method.
    J Gen Physiol. 1988 Aug;92(2):145-59 PMID: 2459299
  28. Divergent pharmacological effects of three calmodulin antagonists, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), chlorpromazine and calmidazolium, on isometric tension development and myosin light chain phosphorylation in intact bovine tracheal smooth muscle.
    J Pharmacol Exp Ther. 1989 Nov;251(2):764-73 PMID: 2810127
  29. Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme.
    Proc Natl Acad Sci U S A. 1990 Jan;87(2):682-5 PMID: 1689048
  30. Inhibition of forskolin-induced neurite outgrowth and protein phosphorylation by a newly synthesized selective inhibitor of cyclic AMP-dependent protein kinase, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), of PC12D pheochromocytoma cells.
    J Biol Chem. 1990 Mar 25;265(9):5267-72 PMID: 2156866
  31. Interleukin 1 induces prolonged L-arginine-dependent cyclic guanosine monophosphate and nitrite production in rat vascular smooth muscle cells.
    J Clin Invest. 1991 Feb;87(2):602-8 PMID: 1671393
  32. Ca2+ current is regulated by cyclic GMP-dependent protein kinase in mammalian cardiac myocytes.
    Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1197-201 PMID: 1705030
  33. Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo.
    Br J Pharmacol. 1990 Nov;101(3):746-52 PMID: 1706208
  34. Neuronal NADPH diaphorase is a nitric oxide synthase.
    Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2811-4 PMID: 1707173
  35. Complexes of .NO with nucleophiles as agents for the controlled biological release of nitric oxide. Vasorelaxant effects.
    J Med Chem. 1991 Nov;34(11):3242-7 PMID: 1956043
  36. S-nitrosylation of proteins with nitric oxide: synthesis and characterization of biologically active compounds.
    Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):444-8 PMID: 1346070
  37. Control of cardiac muscle cell function by an endogenous nitric oxide signaling system.
    Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):347-51 PMID: 7678347
  38. Effect of isoprenaline on I(f) current in latent pacemaker cells isolated from cat right atrium: ruptured vs. perforated patch whole-cell recording methods.
    Pflugers Arch. 1993 Jun;423(5-6):442-7 PMID: 7688892
  39. Nitric oxide in the sensory function of the carotid body.
    Brain Res. 1993 Oct 15;625(1):16-22 PMID: 7694772
  40. Nitric oxide regulates cardiac Ca2+ current. Involvement of cGMP-inhibited and cGMP-stimulated phosphodiesterases through guanylyl cyclase activation.
    J Biol Chem. 1993 Dec 15;268(35):26286-95 PMID: 7902837
  41. Novel actions of methylene blue.
    Eur Heart J. 1993 Nov;14 Suppl I:22-6 PMID: 7507438
  42. Guanylate-cyclase-mediated inhibition of cardiac ICa by carbachol and sodium nitroprusside.
    Pflugers Arch. 1994 Mar;426(5):419-26 PMID: 7517032
  43. An obligatory role for nitric oxide in autonomic control of mammalian heart rate.
    J Physiol. 1994 Apr 15;476(2):309-14 PMID: 7913969
  44. Nitric oxide donor SIN-1 inhibits mammalian cardiac calcium current through cGMP-dependent protein kinase.
    Am J Physiol. 1995 Jan;268(1 Pt 1):C45-54 PMID: 7530909
  45. Nitric oxide synthase (NOS3)-mediated cholinergic modulation of Ca2+ current in adult rabbit atrioventricular nodal cells.
    Circ Res. 1996 Jun;78(6):998-1008 PMID: 8635250
Article Info
Journal
The Journal of general physiology
Abbr.
J Gen Physiol
ISSN
0022-1295
DOI
10.1085/jgp.111.1.113
Published
1998-01-00
Pages
113-25
Language
English
Region
United States
NLM ID
2985110R
PMCID
PMC1887767
Subset
IM
Grants
NHLBI NIH HHS · HL-27652 · United States
External Links
PubMed source DOI: 10.1085/jgp.111.1.113 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