↓ Skip to main content

NCX-Mediated Subcellular Ca2+ Dynamics Underlying Early Afterdepolarizations in LQT2 Cardiomyocytes

Overview of attention for article published in Biophysical Journal, September 2018
Altmetric Badge

About this Attention Score

  • Average Attention Score compared to outputs of the same age
  • Average Attention Score compared to outputs of the same age and source

Mentioned by

twitter
2 tweeters
video
1 video uploader

Citations

dimensions_citation
6 Dimensions

Readers on

mendeley
6 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
NCX-Mediated Subcellular Ca2+ Dynamics Underlying Early Afterdepolarizations in LQT2 Cardiomyocytes
Published in
Biophysical Journal, September 2018
DOI 10.1016/j.bpj.2018.08.004
Pubmed ID
Authors

Mingwang Zhong, Colin M. Rees, Dmitry Terentyev, Bum-Rak Choi, Gideon Koren, Alain Karma

Abstract

Long QT syndrome type 2 (LQT2) is a congenital disease characterized by loss of function mutations in hERG potassium channels (IKr). LQT2 is associated with fatal ventricular arrhythmias promoted by triggered activity in the form of early afterdepolarizations (EADs). We previously demonstrated that intracellular Ca2+ handling is remodeled in LQT2 myocytes. Remodeling leads to aberrant late RyR-mediated Ca2+ releases that drive forward-mode Na+-Ca2+ exchanger (NCX) current and slow repolarization to promote reopening of L-type calcium channels and EADs. Forward-mode NCX was found to be enhanced despite the fact that these late releases do not significantly alter the whole-cell cytosolic calcium concentration during a vulnerable period of phase 2 of the action potential corresponding to the onset of EADs. Here, we use a multiscale ventricular myocyte model to explain this finding. We show that because the local NCX current is a saturating nonlinear function of the local submembrane calcium concentration, a larger number of smaller-amplitude discrete Ca2+ release events can produce a large increase in whole-cell forward-mode NCX current without increasing significantly the whole-cell cytosolic calcium concentration. Furthermore, we develop novel insights, to our knowledge, into how alterations of stochastic RyR activity at the single-channel level cause late aberrant Ca2+ release events. Experimental measurements in transgenic LTQ2 rabbits confirm the critical arrhythmogenic role of NCX and identify this current as a potential target for antiarrhythmic therapies in LQT2.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 6 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 6 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 2 33%
Researcher 2 33%
Student > Postgraduate 1 17%
Unknown 1 17%
Readers by discipline Count As %
Agricultural and Biological Sciences 2 33%
Pharmacology, Toxicology and Pharmaceutical Science 1 17%
Sports and Recreations 1 17%
Medicine and Dentistry 1 17%
Unknown 1 17%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 September 2018.
All research outputs
#7,616,793
of 13,530,536 outputs
Outputs from Biophysical Journal
#4,357
of 6,742 outputs
Outputs of similar age
#132,224
of 268,583 outputs
Outputs of similar age from Biophysical Journal
#43
of 80 outputs
Altmetric has tracked 13,530,536 research outputs across all sources so far. This one is in the 42nd percentile – i.e., 42% of other outputs scored the same or lower than it.
So far Altmetric has tracked 6,742 research outputs from this source. They receive a mean Attention Score of 4.2. This one is in the 34th percentile – i.e., 34% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 268,583 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 48th percentile – i.e., 48% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 80 others from the same source and published within six weeks on either side of this one. This one is in the 41st percentile – i.e., 41% of its contemporaries scored the same or lower than it.