Evidence map›Paper›PMID 16505146›Full record

ArticleThe Journal of general physiology2006

EGFR kinase regulates volume-sensitive chloride current elicited by integrin stretch via PI-3K and NADPH oxidase in ventricular myocytes.

David M Browe, Clive M Baumgarten

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of general physiology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

36 citing papers in PubMed, 90 citations in OpenAlex.

  1. Article
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  12. Mechanisms of I/R-Induced Endothelium-Dependent Vasodilator Dysfunction.Advances in pharmacology (San Diego, Calif.) · 2018
    Review
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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

2 authors at 2 institutions in 2 countries.

David M BroweDepartment of Physiology, Medical College of Virginia, Virginia Commonwealth University, Richmond, 23298, USA.
Clive M Baumgarten
Czech Academy of Sciences, Institute of Physiology · CZVirginia Commonwealth University Medical Center · US

Funding

CARDIAC CELL VOLUME REGULATION IN HEALTH AND DISEASER01HL046764 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI BAUMGARTEN, CLIVE M · 1991 to 2004
$1.4M
SWELLING ACTIVATED CURRENTS AND MYOCYTE VOLUME IN CHFR01HL065435 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI BAUMGARTEN, CLIVE M · 2000 to 2004
$1.2M
NHLBI NIH HHS HL46764NHLBI NIH HHS HL65435NHLBI NIH HHS R01 HL046764NHLBI NIH HHS R01 HL065435
6 · The paper itself

Abstract

Stretch of beta1 integrins activates an outwardly rectifying, tamoxifen-sensitive Cl(-) current (Cl(-) SAC) via AT1 receptors, NADPH oxidase, and reactive oxygen species, and Cl(-) SAC resembles the volume-sensitive Cl(-) current (I(Cl,swell)). Epidermal growth factor receptor (EGFR) kinase undergoes transactivation upon stretch, integrin engagement, and AT1 receptor activation and, in turn, stimulates NADPH oxidase. Therefore, we tested whether Cl(-) SAC is regulated by EGFR kinase signaling and is volume sensitive. Paramagnetic beads coated with mAb for beta1 integrin were attached to myocytes and pulled with an electromagnet. Stretch activated a Cl(-) SAC that was 1.13 +/- 0.10 pA/pF at +40 mV. AG1478 (10 muM), an EGFR kinase blocker, inhibited 93 +/- 13% of Cl(-) SAC, and intracellular pretreatment with 1 muM AG1478 markedly suppressed Cl(-) SAC activation. EGF (3.3 nM) directly activated an outwardly rectifying Cl(-) current (0.81 +/- 0.05 pA/pF at +40 mV) that was fully blocked by 10 muM tamoxifen, an I(Cl,swell) blocker. Phosphatidylinositol 3-kinase (PI-3K) is downstream of EGFR kinase. Wortmannin (500 nM) and LY294002 (100 microM), blockers of PI-3K, inhibited Cl(-) SAC by 67 +/- 6% and 91 +/- 25% respectively, and the EGF-induced Cl(-) current also was fully blocked by LY294002. Furthermore, gp91ds-tat (500 nM), a cell-permeable, chimeric peptide that specifically blocks NADPH oxidase assembly, profoundly inhibited the EGF-induced Cl(-) current. Inactive permeant and active impermeant control peptides had no effect. Myocyte shrinkage with hyperosmotic bathing media inhibited the Cl(-) SAC and EGF-induced Cl(-) current by 88 +/- 9% and 127 +/- 11%, respectively. These results suggest that beta1 integrin stretch activates Cl(-) SAC via EGFR, PI-3K, and NADPH oxidase, and that both the Cl(-) SAC and the EGF-induced Cl(-) currents are likely to be the volume-sensitive Cl(-) current, I(Cl,swell).

Indexed as

AnimalsCells, CulturedCell SizeChloride ChannelsChlorineErbB ReceptorsFemaleHeart VentriclesIntegrin beta1Ion Channel GatingMaleMechanotransduction, CellularMyocytes, CardiacNADPH OxidasesPhosphatidylinositol 3-KinasesRabbitsChloride ChannelsChlorineErbB ReceptorsIntegrin beta1NADPH OxidasesPhosphatidylinositol 3-Kinases

Identifiers

PMID16505146
PMCPMC2151502
OpenAlexW2137492918

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.