Evidence map›Paper›PMID 11691864›Full record

ArticleThe Journal of physiology2001

ACh-induced rebound stimulation of L-type Ca(2+) current in guinea-pig ventricular myocytes, mediated by Gbetagamma-dependent activation of adenylyl cyclase.

A E Belevych, C Sims, R D Harvey

Open access · greenAbstract read
In one paragraph

Article in The Journal of physiology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
0.9field-weighted citation impact, top 26% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 39 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Review
  6. The Roles of Cardiovascular HFrontiers in pharmacology · 2021
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Regulation by Ca2+-signaling pathways of adenylyl cyclases.Cold Spring Harbor perspectives in biology · 2011
    Review
  13. Cytoplasmic cAMP concentrations in intact cardiac myocytes.American journal of physiology. Cell physiology · 2008
    Article
  14. Nuclear localization of Myomesin-1: possible functions.Journal of muscle research and cell motility · 2008
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Muscarinic regulation of cardiac ion channels.British journal of pharmacology · 2003
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

A E BelevychDepartment of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106-4970, USA.
C Sims
R D Harvey
Case Western Reserve University · US

Funding

Muscarinic Signaling Pathways Affecting Cardiac ChannelsR01HL068170 · NHLBI · CASE WESTERN RESERVE UNIVERSITY · PI HARVEY, ROBERT D · 2001 to 2004
$1.1M
ALPHA ADRENERGIC REGULATION OF CARDIAC ION CHANNELSR01AG016658 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI HARVEY, ROBERT D · 1998 to 2000
$217k
NHLBI NIH HHS HL68170NHLBI NIH HHS R01 HL068170NIA NIH HHS AG16658
6 · The paper itself

Abstract

1. The effects that muscarinic receptor stimulation have on the cAMP-dependent regulation of L-type Ca(2+) currents were studied in isolated guinea-pig ventricular myocytes using the whole-cell configuration of the patch-clamp technique. 2. The muscarinic agonist ACh inhibited the Ca(2+) current stimulated by the beta-adrenergic agonist isoprenaline (Iso), and washout of ACh revealed a stimulatory response that appeared as a transient rebound increase in the amplitude of the Ca(2+) current. The ACh-induced stimulatory effect was not observed in the absence of Iso. 3. ACh-induced rebound stimulation was also observed in the presence of H(2) histamine receptor activation and cholera toxin treatment, which like beta-adrenergic receptor activation enhance adenylyl cyclase (AC) activity in a stimulatory G protein (G(s))-dependent manner. ACh-induced rebound stimulation was not observed in the presence of forskolin, which enhances AC activity in a G(s)-independent manner. 4. Pertussis toxin (PTX) treatment blocked both the stimulatory and inhibitory effects of ACh. Intracellular dialysis with QEHA, a peptide that binds free G protein betagamma subunits, selectively antagonized the stimulatory effect, leaving an enhanced inhibitory effect. 5. Evidence for the expression of AC4, an isoform of AC that can be stimulated by Gbetagamma but only in the presence of Galpha(s), was obtained by Western blot analysis of guinea-pig ventricular myocyte membrane preparations. 6. These results suggest that muscarinic receptor stimulation facilitates as well as inhibits cAMP-dependent regulation of the Ca(2+) current and that the net response is a balance between these two actions. We suggest that the stimulatory effect is due to a direct activation of AC4 by the betagamma subunits of a PTX-sensitive G protein.

Indexed as

3',5'-Cyclic-AMP PhosphodiesterasesAcetylcholineAdenylate Cyclase ToxinAdenylyl CyclasesAnimalsCalcium Channel AgonistsCalcium Channels, L-TypeCyclic Nucleotide Phosphodiesterases, Type 3Electric StimulationEnzyme ActivationGTP-Binding Protein alpha Subunits, GsGuinea PigsHeart VentriclesImmunoblottingIn Vitro TechniquesMembrane Potentials3',5'-Cyclic-AMP PhosphodiesterasesAcetylcholineAdenylate Cyclase ToxinAdenylyl CyclasesCalcium Channel AgonistsCalcium Channels, L-TypeCyclic Nucleotide Phosphodiesterases, Type 3GTP-Binding Protein alpha Subunits, GsMuscarinic AgonistsNitric Oxide SynthasePertussis ToxinReceptors, Adrenergic, betaVirulence Factors, Bordetella

Identifiers

PMID11691864
PMCPMC2278900
OpenAlexW2167137030

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.