Evidence map›Paper›PMID 17765619›Full record

ArticleHeart rhythm2007

Protein kinase Cepsilon mediates salutary effects on electrical coupling induced by ischemic preconditioning.

Thomas J Hund, Deborah L Lerner, Kathryn A Yamada, Richard B Schuessler, Jeffrey E Saffitz

Open access · greenAbstract read
In one paragraph

Article in Heart rhythm, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
1.6field-weighted citation impact, top 18% 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

26 citing papers in PubMed, 51 citations in OpenAlex.

  1. Guidelines for assessment of cardiac electrophysiology and arrhythmias in small animals.American journal of physiology. Heart and circulatory physiology · 2022
    Review
  2. Article
  3. Review
  4. Review
  5. The lipidated connexin mimetic peptide SRPTEKT-American journal of physiology. Cell physiology · 2019
    Article
  6. Article
  7. Article
  8. PKC and PKN in heart disease.Journal of molecular and cellular cardiology · 2019
    Review
  9. Review
  10. Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. A new approach for resolution of complex tissue impedance spectra in hearts.IEEE transactions on bio-medical engineering · 2013
    Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Thomas J HundDepartment of Surgery, School of Medicine, Washington University, St. Louis, Missouri, USA.
Deborah L Lerner
Kathryn A Yamada
Richard B Schuessler
Jeffrey E Saffitz
Washington University in St. Louis · USBoston Children's Hospital · US

Funding

STRUCTURAL &ELECTRICAL REMODELING OF CARDIAC CONNEXIN45R01HL066350 · NHLBI · WASHINGTON UNIVERSITY · PI YAMADA, KATHRYN A · 2000 to 2008
$2.9M
REGULATION OF MYOCARDIAL GAP JUNCTIONSR01HL050598 · NHLBI · WASHINGTON UNIVERSITY · PI SAFFITZ, JEFFREY E · 1995 to 2006
$2.3M
PKC signalling and cell-cell communicationF32HL084979 · NHLBI · WASHINGTON UNIVERSITY · PI HUND, THOMAS J · 2006 to 2006
$46k
NHLBI NIH HHS F32 HL084979NHLBI NIH HHS HL066350NHLBI NIH HHS HL084979NHLBI NIH HHS HL50598NHLBI NIH HHS R01 HL050598NHLBI NIH HHS R01 HL066350
6 · The paper itself

Abstract

backgroundIschemic preconditioning delays the onset of electrical uncoupling and prevents loss of the primary ventricular gap junction protein connexin 43 (Cx43) from gap junctions during subsequent ischemia.

objectiveTo test the hypothesis that these effects are mediated by protein kinase C epsilon (PKCepsilon), we studied isolated Langendorff-perfused hearts from mice with homozygous germline deletion of PKCepsilon (PKCepsilon-KO).

methodsCx43 phosphorylation and distribution were measured by quantitative immunoblotting and confocal microscopy. Changes in electrical coupling were monitored using the 4-electrode technique to measure whole-tissue resistivity.

resultsThe amount of Cx43 located in gap junctions, measured by confocal microscopy under basal conditions, was significantly greater in PKCepsilon-KO hearts compared with wild-type, but total Cx43 content measured by immunoblotting was not different. These unanticipated results indicate that PKCepsilon regulates subcellular distribution of Cx43 under normal conditions. Preconditioning prevented loss of Cx43 from gap junctions during ischemia in wild-type but not PKCepsilon-KO hearts. Specific activation of PKCepsilon, but not PKCdelta, also prevented ischemia-induced loss of Cx43 from gap junctions. Preconditioning delayed the onset of uncoupling in wild-type but hastened uncoupling in PKCepsilon-KO hearts. Cx43 phosphorylation at the PKC site Ser368 increased 5-fold after ischemia in wild-type hearts, and surprisingly, by nearly 10-fold in PKCepsilon-KO hearts. Preconditioning prevented phosphorylation of Cx43 in gap junction plaques at Ser368 in wild-type but not PKCepsilon-KO hearts.

conclusionTaken together, these results indicate that PKCepsilon plays a critical role in preconditioning to preserve Cx43 signal in gap junctions and delay electrical uncoupling during ischemia.

Indexed as

Ischemic Preconditioning, MyocardialAnimalsConnexin 43Electric ImpedanceGap JunctionsMiceMice, Inbred C57BLMice, KnockoutModels, AnimalMyocardial IschemiaMyocardial ReperfusionPhosphorylationProtein Kinase C-epsilonProtein TransportRabbitsConnexin 43GJA1 protein, humanProtein Kinase C-epsilon

Identifiers

PMID17765619
PMCPMC2711555
OpenAlexW1970105142

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.