Home LiteratureArticle Details
PMID: 2445960 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Calcium channel currents and their inhibition by (-)-baclofen in rat sensory neurones: modulation by guanine nucleotides.

The Journal of physiology ·Vol. 386 ·1987-05-00 ·Pages 1-17

Dolphin AC, Scott RH

Abstract

1. The effect of intracellular application of the hydrolysis-resistant GTP and GDP analogues, guanosine 5'-O-3-thiotriphosphate (GTP-gamma-S), and guanosine 5'-O-2-thiodiphosphate (GDP-beta-S) has been examined on voltage-activated calcium-channel currents and the ability of the gamma-aminobutyric acid B agonist baclofen to inhibit them, in cultured rat dorsal root ganglion (d.r.g.) neurones. 2. Under control conditions, the calcium-channel current, recorded using the whole-cell patch technique with Ba2+ rather than Ca2+ as the permeant divalent cation, consists of an inactivating and a sustained current. In the presence of 500 microM-GTP-gamma-S included in the patch pipette, the calcium-channel current was activated more slowly and was largely non-inactivating during the 100 ms depolarization voltage step. The effects of GTP-gamma-S were abolished by pre-treatment of cells with pertussis toxin. 3. The calcium-channel current recorded in the presence of 500 microM-GDP-beta-S had a more marked transient component than the control calcium-channel current. The proportion of transient calcium-channel current in the presence of GDP-beta-S was not reduced in Na+-free medium. 4. No statistically significant effects of GTP-gamma-S and GDP-beta-S were observed on the calcium-activated potassium current IK(Ca), the transient outward potassium current activated in Ca2+-free medium, or on the inwardly rectifying current (Ih) activated by hyperpolarization. 5. GTP-gamma-S increased the ability of baclofen to inhibit calcium-channel currents, whereas this was decreased by GDP-beta-S and by pre-treatment of cells with pertussis toxin. The half-maximal effective dose (EC50) for baclofen was 2 microM in the presence of GTP-gamma-S, 15 microM for control and 50 microM in the presence of GDP-beta-S. Comparable results were obtained using a single concentration of the adenosine agonist 2-chloroadenosine (2-CA, 0.05 microM) to inhibit calcium-channel currents; its effect was significantly increased by GTP-gamma-S and reduced by GDP-beta-S. 6. The ability of baclofen to inhibit calcium-channel currents was not affected by 1 microM-forskolin or 50 microM-intracellular cyclic AMP. 7. It is concluded that calcium channels in d.r.g.s are associated with a nucleotide binding protein, and that this mediates the effect of baclofen and 2-CA on calcium-channel currents. The ability of GTP-gamma-S to inhibit the transient component of calcium-channel currents in the absence of agonist may represent a means of differentially regulating calcium-channel activity.

MeSH Terms
Action Potentials/drug effects Animals Baclofen/pharmacology Calcium/physiology Cells, Cultured Depression, Chemical Dose-Response Relationship, Drug Ganglia, Spinal/physiology Guanine Nucleotides/pharmacology Ion Channels/drug effects Neurons, Afferent/physiology Pertussis Toxin Rats Time Factors Virulence Factors, Bordetella/pharmacology
Chemicals
Guanine Nucleotides Ion Channels Virulence Factors, Bordetella Pertussis Toxin Baclofen Calcium
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Dolphin A C
Department of Pharmacology, St George's Hospital Medical School, London.
Scott R H
References (44)
44 references, click to expand
  1. Pertussis toxin substrate, the putative Ni component of adenylyl cyclases, is an alpha beta heterodimer regulated by guanine nucleotide and magnesium.
    Proc Natl Acad Sci U S A. 1983 Jul;80(14):4276-80 PMID: 6308612
  2. Ca2+ channel modulation by 8-bromocyclic AMP in cultured heart cells.
    Nature. 1983 Aug 4-10;304(5925):462-4 PMID: 6308462
  3. Reconstitution of catecholamine-stimulated guanosinetriphosphatase activity.
    Biochemistry. 1983 Sep 13;22(19):4357-62 PMID: 6138091
  4. Guanine nucleotide-binding regulatory proteins and dual control of adenylate cyclase.
    J Clin Invest. 1984 Jan;73(1):1-4 PMID: 6140270
  5. Inhibition of GABAB receptor binding by guanyl nucleotides.
    J Neurochem. 1984 Mar;42(3):652-7 PMID: 6319603
  6. Beta-adrenergic modulation of calcium channels in frog ventricular heart cells.
    Nature. 1984 Jan 26-Feb 1;307(5949):371-5 PMID: 6320002
  7. Inositol phospholipid hydrolysis in rat cerebral cortical slices: I. Receptor characterisation.
    J Neurochem. 1984 May;42(5):1379-87 PMID: 6323632
  8. gamma-aminobutyric acid B receptors are negatively coupled to adenylate cyclase in brain, and in the cerebellum these receptors may be associated with granule cells.
    Mol Pharmacol. 1984 Jan;25(1):24-8 PMID: 6323949
  9. Inositol trisphosphate, a novel second messenger in cellular signal transduction.
    Nature. 1984 Nov 22-28;312(5992):315-21 PMID: 6095092
  10. Patch-clamp study of the tetrodotoxin-resistant sodium current in group C sensory neurones.
    Neurosci Lett. 1984 Oct 12;51(2):241-6 PMID: 6096775
  11. Specificity of the functional interactions of the beta-adrenergic receptor and rhodopsin with guanine nucleotide regulatory proteins reconstituted in phospholipid vesicles.
    J Biol Chem. 1985 Feb 10;260(3):1493-500 PMID: 2981858
  12. Enhancement of calcium current in Aplysia neurones by phorbol ester and protein kinase C.
    Nature. 1985 Jan 24-30;313(6000):313-6 PMID: 2578617
  13. GABAB-receptor-activated K+ current in voltage-clamped CA3 pyramidal cells in hippocampal cultures.
    Proc Natl Acad Sci U S A. 1985 Mar;82(5):1558-62 PMID: 2983351
  14. Potential role for a guanine nucleotide regulatory protein in chemoattractant receptor mediated polyphosphoinositide metabolism, Ca++ mobilization and cellular responses by leukocytes.
    Biochem Biophys Res Commun. 1985 Mar 15;127(2):450-7 PMID: 2983721
  15. Role of guanine nucleotide binding protein in the activation of polyphosphoinositide phosphodiesterase.
    Nature. 1985 Apr 11-17;314(6011):534-6 PMID: 2986003
  16. Modulation of calcium channels by norepinephrine in internally dialyzed avian sensory neurons.
    J Gen Physiol. 1985 May;85(5):743-63 PMID: 2582078
  17. Two types of calcium channels in the somatic membrane of new-born rat dorsal root ganglion neurones.
    J Physiol. 1985 Feb;359:431-46 PMID: 2582115
  18. Pertussis toxin does not inhibit muscarinic-receptor-mediated phosphoinositide hydrolysis or calcium mobilization.
    Biochem J. 1985 May 1;227(3):933-7 PMID: 2988509
  19. gamma-Aminobutyric acid-induced depression of calcium currents of chick sensory neurons.
    Neurosci Lett. 1985 May 14;56(2):205-10 PMID: 2409484
  20. Three types of neuronal calcium channel with different calcium agonist sensitivity.
    Nature. 1985 Aug 1-7;316(6027):440-3 PMID: 2410796
  21. Nucleoside phosphorothioates.
    Annu Rev Biochem. 1985;54:367-402 PMID: 2411211
  22. Functional reconstitution of purified muscarinic receptors and inhibitory guanine nucleotide regulatory protein.
    Nature. 1985 Aug 22-28;316(6030):731-3 PMID: 3929139
  23. The possible modulation of the development of rat dorsal root ganglion cells by the presence of 5-HT-containing neurones of the brainstem in dissociated cell culture.
    Brain Res. 1985 Sep;354(1):55-65 PMID: 2994852
  24. Prevention of the agonist binding to gamma-aminobutyric acid B receptors by guanine nucleotides and islet-activating protein, pertussis toxin, in bovine cerebral cortex. Possible coupling of the toxin-sensitive GTP-binding proteins to receptors.
    J Biol Chem. 1985 Oct 15;260(23):12653-8 PMID: 2995384
  25. GTP-binding proteins couple cardiac muscarinic receptors to a K channel.
    Nature. 1985 Oct 10-16;317(6037):536-8 PMID: 2413367
  26. Uncoupling of cardiac muscarinic and beta-adrenergic receptors from ion channels by a guanine nucleotide analogue.
    Nature. 1985 Oct 10-16;317(6037):538-40 PMID: 2413368
  27. Kinase C activator 1,2-oleoylacetylglycerol attenuates voltage-dependent calcium current in sensory neurons.
    Proc Natl Acad Sci U S A. 1986 Jan;83(1):184-8 PMID: 2417236
  28. Ca2+ release from endoplasmic reticulum is mediated by a guanine nucleotide regulatory mechanism.
    Nature. 1986 Apr 3-9;320(6061):461-4 PMID: 2421167
  29. Inhibition of calcium currents in cultured rat dorsal root ganglion neurones by (-)-baclofen.
    Br J Pharmacol. 1986 May;88(1):213-20 PMID: 2423173
  30. Effect of internal calcium concentration on calcium currents in rat sensory neurones.
    Pflugers Arch. 1986 Apr;406(4):433-5 PMID: 2423955
  31. Calcium-dependent currents in cultured rat dorsal root ganglion neurones are inhibited by an adenosine analogue.
    J Physiol. 1986 Apr;373:47-61 PMID: 2427698
  32. Regulation of calcium currents by a GTP analogue: potentiation of (-)-baclofen-mediated inhibition.
    Neurosci Lett. 1986 Aug 15;69(1):59-64 PMID: 2427978
  33. Activation of pigeon erythrocyte membrane adenylate cyclase by guanylnucleotide analogues and separation of a nucleotide binding protein.
    J Biol Chem. 1975 Feb 10;250(3):867-76 PMID: 1120776
  34. Catecholamine-stimulated GTPase activity in turkey erythrocyte membranes.
    Biochim Biophys Acta. 1976 Dec 8;452(2):538-51 PMID: 188466
  35. Guanosine 5'-O-(2-thiodiphosphate). An inhibitor of adenylate cyclase stimulation by guanine nucleotides and fluoride ions.
    J Biol Chem. 1979 Oct 10;254(19):9829-34 PMID: 489574
  36. The role of hormone receptors and GTP-regulatory proteins in membrane transduction.
    Nature. 1980 Mar 6;284(5751):17-22 PMID: 6101906
  37. Differential regulation of the alpha 2-adrenergic receptor by Na+ and guanine nucleotides.
    Nature. 1980 Dec 25;288(5792):709-11 PMID: 6256638
  38. 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
  39. Two types of gamma-aminobutyric acid receptor on embryonic sensory neurones.
    Br J Pharmacol. 1981 Nov;74(3):579-85 PMID: 6271320
  40. Ionic currents in the somatic membrane of rat dorsal root ganglion neurons-I. Sodium currents.
    Neuroscience. 1981;6(12):2423-30 PMID: 6275294
  41. Occurrence of an inhibitory guanine nucleotide-binding regulatory component of the adenylate cyclase system in cyc- variants of S49 lymphoma cells.
    Eur J Biochem. 1983 Feb 15;130(3):605-11 PMID: 6297910
  42. A nucleotide regulatory site for somatostatin inhibition of adenylate cyclase in S49 lymphoma cells.
    Nature. 1983 May 12-18;303(5913):177-8 PMID: 6133220
  43. The regulatory components of adenylate cyclase and transducin. A family of structurally homologous guanine nucleotide-binding proteins.
    J Biol Chem. 1983 Jun 10;258(11):7059-63 PMID: 6304074
  44. A voltage-clamp analysis of inward (anomalous) rectification in mouse spinal sensory ganglion neurones.
    J Physiol. 1983 Jul;340:19-45 PMID: 6887047
Article Info
Journal
The Journal of physiology
Abbr.
J Physiol
ISSN
0022-3751
DOI
10.1113/jphysiol.1987.sp016518
Published
1987-05-00
Pages
1-17
Language
English
Region
England
NLM ID
0266262
PMCID
PMC1192446
Subset
IM
External Links
PubMed source DOI: 10.1113/jphysiol.1987.sp016518 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