Evidence map›Paper›PMID 24055949›Full record

ArticleHeart rhythm2013

Electronic "expression" of the inward rectifier in cardiocytes derived from human-induced pluripotent stem cells.

Glenna C L Bett, Aaron D Kaplan, Agnieszka Lis, Thomas R Cimato, Emmanuel S Tzanakakis, Qinlian Zhou, Michael J Morales, Randall L Rasmusson

Abstract read
In one paragraph

Article in Heart rhythm, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
–field-weighted citation impact
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

75 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Biophysical properties of NaScientific reports · 2023
    Article
  7. Article
  8. Effects of NALCN-Encoded NaThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2023
    Article
  9. Review
  10. Pro-arrhythmic effects of gain-of-function potassium channel mutations in the short QT syndrome.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
    Review
  11. Article
  12. Article
  13. Article
  14. Kv12-Encoded KbioRxiv : the preprint server for biology · 2023
    Article
  15. Injection of IFrontiers in physiology · 2023
    Article
  16. Article
  17. Article
  18. Article
  19. Contributions of NaScientific reports · 2021
    Article
  20. Article

15 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Glenna C L BettObstetrics and Gynecology; Physiology and Biophysics. Electronic address: bett@buffalo.edu.
Aaron D Kaplan
Agnieszka Lis
Thomas R Cimato
Emmanuel S Tzanakakis
Qinlian Zhou
Michael J Morales
Randall L Rasmusson

Funding

Markov Models of Potassium Channel GatingR01HL062465 · NHLBI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI RASMUSSON, RANDALL L. · 1998 to 2012
$3.5M
Bioprocess for cardiac cell generation from human induced pluripotent stem cellsR01HL103709 · NHLBI · TUFTS UNIVERSITY MEDFORD · PI TZANAKAKIS, EMMANOUHL · 2011 to 2014
$1.5M
Sex Differences in Molecular Heterogeneity of Cardiac RepolarizationR21HL093631 · NHLBI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI BETT, GLENNA C L · 2011 to 2012
$429k
Myocardial Properties of Timothy SyndromeR21HL088058 · NHLBI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI RASMUSSON, RANDALL L. · 2008 to 2009
$413k
NHLBI NIH HHS HL062465NHLBI NIH HHS HL088058NHLBI NIH HHS HL093631NHLBI NIH HHS HL103709NHLBI NIH HHS R01 HL062465NHLBI NIH HHS R01 HL103709NHLBI NIH HHS R21 HL088058NHLBI NIH HHS R21 HL093631
6 · The paper itself

Abstract

backgroundHuman-induced pluripotent stem cell (h-iPSC)-derived cardiac myocytes are a unique model in which human myocyte function and dysfunction are studied, especially those from patients with genetic disorders. They are also considered a major advance for drug safety testing. However, these cells have considerable unexplored potential limitations when applied to quantitative action potential (AP) analysis. One major factor is spontaneous activity and resulting variability and potentially anomalous behavior of AP parameters.

objectiveTo demonstrate the effect of using an in silico interface on electronically expressed I(K1), a major component lacking in h-iPSC-derived cardiac myocytes.

methodsAn in silico interface was developed to express synthetic I(K1) in cells under whole-cell voltage clamp.

resultsElectronic I(K1) expression established a physiological resting potential, eliminated spontaneous activity, reduced spontaneous early and delayed afterdepolarizations, and decreased AP variability. The initiated APs had the classic rapid upstroke and spike and dome morphology consistent with data obtained with freshly isolated human myocytes as well as the readily recognizable repolarization attributes of ventricular and atrial cells. The application of 1 µM of BayK-8644 resulted in anomalous AP shortening in h-iPSC-derived cardiac myocytes. When I(K1) was electronically expressed, BayK-8644 prolonged the AP, which is consistent with the existing results on native cardiac myocytes.

conclusionsThe electronic expression of I(K1) is a simple and robust method to significantly improve the physiological behavior of the AP and electrical profile of h-iPSC-derived cardiac myocytes. Increased stability enables the use of this preparation for a controlled quantitative analysis of AP parameters, for example, drug responsiveness, genetic disorders, and dynamic behavior restitution profiles.

Indexed as

Action PotentialsArrhythmias, CardiacCalcium Channels, L-TypeCells, CulturedHumansInduced Pluripotent Stem CellsMyocytes, CardiacPatch-Clamp TechniquesCalcium Channels, L-Typeaction potentialaction potential durationAPAPDArrhythmiacalcium currentDADdelayed afterdepolarizationdV/dt(max)EADearly afterdepolarizationHearth-iPSChuman-induced pluripotent stem cellI(Ca)I(f)I(K1)I(K1,Synthetic)I(Na)induced pluripotent stem cellinward rectifier potassium currentiPSCI(to)maximum rate of change of voltage with timepacemaker currentPotassium channelRepolarizationsodium currentStem cellsynthetic I(K1)Timothy syndrometransient outward potassium currentTS

Identifiers

PMID24055949
PMCPMC3851822

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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.