Evidence map›Paper›PMID 25070892›Full record

ArticleThe Journal of biological chemistry2014

The angiotensin II type 1 receptor (AT1R) closely interacts with large conductance voltage- and Ca2+-activated K+ (BK) channels and inhibits their activity independent of G-protein activation.

Zhu Zhang, Min Li, Rong Lu, Abderrahmane Alioua, Enrico Stefani, Ligia Toro

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

21 citing papers in PubMed, 31 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Large conductance voltage-and calcium-activated KFrontiers in pharmacology · 2024
    Review
  5. Loss of IP3R-BKInternational journal of molecular sciences · 2023
    Article
  6. Article
  7. Increased ATHypertension research : official journal of the Japanese Society of Hypertension · 2021
    Article
  8. Article
  9. Coronary Large Conductance CaFrontiers in physiology · 2021
    Review
  10. Review
  11. Article
  12. Article
  13. Calcium- and voltage-gated BK channels in vascular smooth muscle.Pflugers Archiv : European journal of physiology · 2018
    Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. 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

6 authors at 1 institution in 1 country.

Zhu ZhangFrom the Departments of Anesthesiology.
Min LiFrom the Departments of Anesthesiology.
Rong LuFrom the Departments of Anesthesiology.
Abderrahmane AliouaFrom the Departments of Anesthesiology.
Enrico StefaniFrom the Departments of Anesthesiology, Physiology, the Brain Research Institute, and the Cardiovascular Research Laboratory, University of California, Los Angeles, California 90095.
Ligia ToroFrom the Departments of Anesthesiology, the Brain Research Institute, and the Cardiovascular Research Laboratory, University of California, Los Angeles, California 90095 Molecular and Medical Pharmacology, and ltoro@ucla.edu.
University of California, Los Angeles · US

Funding

Revealing Cardiovascular Stress Regulation beyond the Diffraction LimitR01HL088640 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI STEFANI, ENRICO · 2007 to 2011
$5.3M
BK(Ca) channel in heart mitochondriaR01HL107418 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI OLCESE, RICCARDO, STEFANI, ENRICO · 2012 to 2015
$2.5M
Novel interactions of Slo1 channel and Thromboxane A2 receptor in blood vesselsR01HL096740 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI STEFANI, ENRICO, TORO DE STEFANI, LIGIA G. · 2009 to 2010
$1.3M
NHLBI NIH HHS HL088640NHLBI NIH HHS HL096740NHLBI NIH HHS HL107418NHLBI NIH HHS R01 HL088640NHLBI NIH HHS R01 HL096740NHLBI NIH HHS R01 HL107418
6 · The paper itself

Abstract

Angiotensin II (ANG-II) and BK channels play important roles in the regulation of blood pressure. In arterial smooth muscle, ANG-II inhibits BK channels, but the underlying molecular mechanisms are unknown. Here, we first investigated whether ANG-II utilizes its type 1 receptor (AT1R) to modulate BK activity. Pharmacological, biochemical, and molecular evidence supports a role for AT1R. In renal arterial myocytes, the AT1R antagonist losartan (10 μM) abolished the ANG-II (1 μM)-induced reduction of whole cell BK currents, and BK channels and ANG-II receptors were found to co-localize at the cell periphery. We also found that BK inhibition via ANG-II-activated AT1R was independent of G-protein activation (assessed with 500 μM GDPβS). In BK-expressing HEK293T cells, ANG-II (1 μM) also induced a reduction of BK currents, which was contingent on AT1R expression. The molecular mechanisms of AT1R and BK channel coupling were investigated in co-transfected cells. Co-immunoprecipitation showed formation of a macromolecular complex, and live immunolabeling demonstrated that both proteins co-localized at the plasma membrane with high proximity indexes as in arterial myocytes. Consistent with a close association, we discovered that the sole AT1R expression could decrease BK channel voltage sensitivity. Truncated BK proteins revealed that the voltage-sensing conduction cassette is sufficient for BK-AT1R association. Finally, C-terminal yellow and cyan fluorescent fusion proteins, AT1R-YFP and BK-CFP, displayed robust co-localized Förster resonance energy transfer, demonstrating intermolecular interactions at their C termini. Overall, our results strongly suggest that AT1R regulates BK channels through a close protein-protein interaction involving multiple BK regions and independent of G-protein activation.

Indexed as

Angiotensin IIAngiotensin II Type 1 Receptor BlockersAnimalsCalcium SignalingFluorescence Resonance Energy TransferGreen Fluorescent ProteinsGTP-Binding ProteinsHEK293 CellsHumansLarge-Conductance Calcium-Activated Potassium ChannelsLosartanMuscle CellsPatch-Clamp TechniquesRatsReceptor, Angiotensin, Type 1Renal ArteryAngiotensin IIAngiotensin II Type 1 Receptor BlockersGreen Fluorescent ProteinsGTP-Binding ProteinsLarge-Conductance Calcium-Activated Potassium ChannelsLosartanReceptor, Angiotensin, Type 1Angiotensin IIAngiotensin II Type 1A ReceptorCell Surface ReceptorLarge Conductance Voltage- and Ca2+-activated K+ ChannelPatch ClampPotassium ChannelProtein ComplexVascular Smooth Muscle Cells

Identifiers

PMID25070892
PMCPMC4162171
OpenAlexW2013178091

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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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.