ca2+-clock-dependent pacemaking in the sinus node is impaired in mice with a cardiac specific reduction in serca2 abundance
Clicks: 295
ID: 247764
2016
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This
article has not been analysed, so there is no overall score —
reader engagement is measured and shown alongside.
Reader Engagement
Steady Performance
30.0
/100
295 views
29 readers
AI Quality Assessment
Not analyzed
Readership in this journal
SteadyRanked #136 of 461 articles by views in Journal of clinical and experimental dentistry
Most read
Least read
Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 461 in total.
Mint this article as an NFT
Not yet mintedCreate a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.
5
SUSD
one-off · no wallet required
Abstract
Background: The sarcoplasmic reticulum Ca2+-ATPase (SERCA2) pump is an important component of the Ca2+-clock pacemaker mechanism that provides robustness and flexibility to sinus node pacemaking. We have developed transgenic mice with reduced cardiac SERCA2 abundance (Serca2 KO) as a model for investigating SERCA2’s role in sinus node pacemaking.Methods and Results: In Serca2 KO mice, ventricular SERCA2a protein content measured by Western blotting was 75% (P<0.05) lower than that in control mice (Serca2 FF) tissue. Immunofluorescent labelling of SERCA2a in ventricular, atrial, sinus node periphery and centre tissue sections revealed 46%, 45%, 55% and 34% (all P<0.05 vs. Serca2 FF) lower labelling, respectively and a mosaic pattern of expression. With telemetric ECG surveillance, we observed no difference in basal heart rate, but the PR-interval was prolonged in Serca2 KO mice: 49±1 vs. 40±1 ms (P<0.001) in Serca2 FF. During exercise, heart rate in Serca2 KO mice was elevated to 667±22 bpm, considerably less than 780±17 bpm (P<0.01) in Serca2 FF. In isolated sinus node preparations, 2 mM Cs+ caused bradycardia that was equally pronounced in Serca2 KO and Serca2 FF (32±4% vs. 29±5%), indicating no change in If. Disabling the Ca2+-clock with 2 μM ryanodine induced bradycardia that was less pronounced in Serca2 KO preparations (9±1% vs. 20±3% in Serca2 FF; P<0.05), suggesting a disrupted Ca2+-clock. Mathematical modelling was used to dissect the effects of membrane and Ca2+-clock components on Serca2 KO mouse heart rate and sinus node action potential. Computer modelling predicted a slowing of heart rate with Serca2 downregulation and the heart rate slowing was pronounced at >70% Serca2 downregulation.Conclusions: Serca2 KO mice show a disrupted Ca2+-clock-dependent pacemaker mechanism contributing to impaired sinus node and atrioventricular node function.
Abstract Quality Issue:
This abstract appears to be incomplete or contains metadata (69 words).
Try re-searching for a better abstract.
| Reference Key |
logantha2016frontiersca2+-clock-dependent
Use this key to autocite in the manuscript while using
SciMatic Manuscript Manager or Thesis Manager
|
|---|---|
| Authors | ;Sunil Jit Ramamoorthy Jeewanlal Logantha;Mathis Korseberg Stokke;Mathis Korseberg Stokke;Mathis Korseberg Stokke;Andrew J Atkinson;Sanjay R Kharche;Sajida eParveen;Yawer eSaeed;Ivar eSjaastad;Ivar eSjaastad;Ole M Sejersted;Ole M Sejersted;Halina eDobrzynski |
| Journal | Journal of clinical and experimental dentistry |
| Year | 2016 |
| DOI |
10.3389/fphys.2016.00197
|
| URL | |
| Keywords |
Citations
No citations found. To add a citation, contact the admin at info@scimatic.org
Comments
No comments yet. Be the first to comment on this article.