Evidence map›Paper›PMID 26450916›Full record

ArticleCirculation2015

Direct Evidence for Microdomain-Specific Localization and Remodeling of Functional L-Type Calcium Channels in Rat and Human Atrial Myocytes.

Alexey V Glukhov, Marina Balycheva, Jose L Sanchez-Alonso, Zeki Ilkan, Anita Alvarez-Laviada, Navneet Bhogal, Ivan Diakonov, Sophie Schobesberger, Markus B Sikkel, Anamika Bhargava and 4 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
6.6field-weighted citation impact, top 3% 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

65 citing papers in PubMed, 94 citations in OpenAlex.

  1. Aging Disrupts L-type CaCirculation research · 2026
    Article
  2. Article
  3. Downregulation of L-type CaHeart rhythm · 2026
    Article
  4. Article
  5. Stress-Induced calcium mishandling in cardiac (Patho)physiology.Cellular and molecular life sciences : CMLS · 2025
    Review
  6. Cigarette exposure lights the NLPR3 inflammasome pathway to atrial fibrillation.American journal of physiology. Heart and circulatory physiology · 2025
    Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Caveolae-associated cAMP/CaJournal of molecular and cellular cardiology · 2023
    Article
  14. Article
  15. Mechanisms of spontaneous CaThe Journal of physiology · 2023
    Article
  16. Mechanisms of spontaneous CaThe Journal of physiology · 2023
    Article
  17. Review
  18. Article
  19. Review
  20. Article

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

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

14 authors at 3 institutions in 2 countries.

Alexey V GlukhovFrom Department of Cardiovascular Sciences, National Heart and Lung Institute, Imperial College London, United Kingdom (A.V.G., M.B., J.L.S.-A., Z.I., A.A.-L., N.B., I.D., S.S., M.B.S., A.B., P.P.P., J.G.); University of Verona, School of Medicine, Verona, Italy (M.B., G.F.); Department of Cardiothoracic Surgery, Hammersmith Hospital, National Heart and Lung Institute, Imperial College London, United Kingdom (P.P.P.); and Cardiovascular Research Center and Department of Physiology, Temple University School of Medicine, Philadelphia, PA (S.R.H.).
Marina BalychevaFrom Department of Cardiovascular Sciences, National Heart and Lung Institute, Imperial College London, United Kingdom (A.V.G., M.B., J.L.S.-A., Z.I., A.A.-L., N.B., I.D., S.S., M.B.S., A.B., P.P.P., J.G.); University of Verona, School of Medicine, Verona, Italy (M.B., G.F.); Department of Cardiothoracic Surgery, Hammersmith Hospital, National Heart and Lung Institute, Imperial College London, United Kingdom (P.P.P.); and Cardiovascular Research Center and Department of Physiology, Temple University School of Medicine, Philadelphia, PA (S.R.H.).
Jose L Sanchez-AlonsoFrom Department of Cardiovascular Sciences, National Heart and Lung Institute, Imperial College London, United Kingdom (A.V.G., M.B., J.L.S.-A., Z.I., A.A.-L., N.B., I.D., S.S., M.B.S., A.B., P.P.P., J.G.); University of Verona, School of Medicine, Verona, Italy (M.B., G.F.); Department of Cardiothoracic Surgery, Hammersmith Hospital, National Heart and Lung Institute, Imperial College London, United Kingdom (P.P.P.); and Cardiovascular Research Center and Department of Physiology, Temple University School of Medicine, Philadelphia, PA (S.R.H.).
Zeki IlkanFrom Department of Cardiovascular Sciences, National Heart and Lung Institute, Imperial College London, United Kingdom (A.V.G., M.B., J.L.S.-A., Z.I., A.A.-L., N.B., I.D., S.S., M.B.S., A.B., P.P.P., J.G.); University of Verona, School of Medicine, Verona, Italy (M.B., G.F.); Department of Cardiothoracic Surgery, Hammersmith Hospital, National Heart and Lung Institute, Imperial College London, United Kingdom (P.P.P.); and Cardiovascular Research Center and Department of Physiology, Temple University School of Medicine, Philadelphia, PA (S.R.H.).
Anita Alvarez-LaviadaFrom Department of Cardiovascular Sciences, National Heart and Lung Institute, Imperial College London, United Kingdom (A.V.G., M.B., J.L.S.-A., Z.I., A.A.-L., N.B., I.D., S.S., M.B.S., A.B., P.P.P., J.G.); University of Verona, School of Medicine, Verona, Italy (M.B., G.F.); Department of Cardiothoracic Surgery, Hammersmith Hospital, National Heart and Lung Institute, Imperial College London, United Kingdom (P.P.P.); and Cardiovascular Research Center and Department of Physiology, Temple University School of Medicine, Philadelphia, PA (S.R.H.).
Navneet BhogalFrom Department of Cardiovascular Sciences, National Heart and Lung Institute, Imperial College London, United Kingdom (A.V.G., M.B., J.L.S.-A., Z.I., A.A.-L., N.B., I.D., S.S., M.B.S., A.B., P.P.P., J.G.); University of Verona, School of Medicine, Verona, Italy (M.B., G.F.); Department of Cardiothoracic Surgery, Hammersmith Hospital, National Heart and Lung Institute, Imperial College London, United Kingdom (P.P.P.); and Cardiovascular Research Center and Department of Physiology, Temple University School of Medicine, Philadelphia, PA (S.R.H.).
Ivan DiakonovFrom Department of Cardiovascular Sciences, National Heart and Lung Institute, Imperial College London, United Kingdom (A.V.G., M.B., J.L.S.-A., Z.I., A.A.-L., N.B., I.D., S.S., M.B.S., A.B., P.P.P., J.G.); University of Verona, School of Medicine, Verona, Italy (M.B., G.F.); Department of Cardiothoracic Surgery, Hammersmith Hospital, National Heart and Lung Institute, Imperial College London, United Kingdom (P.P.P.); and Cardiovascular Research Center and Department of Physiology, Temple University School of Medicine, Philadelphia, PA (S.R.H.).
Sophie SchobesbergerFrom Department of Cardiovascular Sciences, National Heart and Lung Institute, Imperial College London, United Kingdom (A.V.G., M.B., J.L.S.-A., Z.I., A.A.-L., N.B., I.D., S.S., M.B.S., A.B., P.P.P., J.G.); University of Verona, School of Medicine, Verona, Italy (M.B., G.F.); Department of Cardiothoracic Surgery, Hammersmith Hospital, National Heart and Lung Institute, Imperial College London, United Kingdom (P.P.P.); and Cardiovascular Research Center and Department of Physiology, Temple University School of Medicine, Philadelphia, PA (S.R.H.).
Markus B SikkelFrom Department of Cardiovascular Sciences, National Heart and Lung Institute, Imperial College London, United Kingdom (A.V.G., M.B., J.L.S.-A., Z.I., A.A.-L., N.B., I.D., S.S., M.B.S., A.B., P.P.P., J.G.); University of Verona, School of Medicine, Verona, Italy (M.B., G.F.); Department of Cardiothoracic Surgery, Hammersmith Hospital, National Heart and Lung Institute, Imperial College London, United Kingdom (P.P.P.); and Cardiovascular Research Center and Department of Physiology, Temple University School of Medicine, Philadelphia, PA (S.R.H.).
Anamika BhargavaFrom Department of Cardiovascular Sciences, National Heart and Lung Institute, Imperial College London, United Kingdom (A.V.G., M.B., J.L.S.-A., Z.I., A.A.-L., N.B., I.D., S.S., M.B.S., A.B., P.P.P., J.G.); University of Verona, School of Medicine, Verona, Italy (M.B., G.F.); Department of Cardiothoracic Surgery, Hammersmith Hospital, National Heart and Lung Institute, Imperial College London, United Kingdom (P.P.P.); and Cardiovascular Research Center and Department of Physiology, Temple University School of Medicine, Philadelphia, PA (S.R.H.).
Giuseppe FaggianFrom Department of Cardiovascular Sciences, National Heart and Lung Institute, Imperial College London, United Kingdom (A.V.G., M.B., J.L.S.-A., Z.I., A.A.-L., N.B., I.D., S.S., M.B.S., A.B., P.P.P., J.G.); University of Verona, School of Medicine, Verona, Italy (M.B., G.F.); Department of Cardiothoracic Surgery, Hammersmith Hospital, National Heart and Lung Institute, Imperial College London, United Kingdom (P.P.P.); and Cardiovascular Research Center and Department of Physiology, Temple University School of Medicine, Philadelphia, PA (S.R.H.).
Prakash P PunjabiFrom Department of Cardiovascular Sciences, National Heart and Lung Institute, Imperial College London, United Kingdom (A.V.G., M.B., J.L.S.-A., Z.I., A.A.-L., N.B., I.D., S.S., M.B.S., A.B., P.P.P., J.G.); University of Verona, School of Medicine, Verona, Italy (M.B., G.F.); Department of Cardiothoracic Surgery, Hammersmith Hospital, National Heart and Lung Institute, Imperial College London, United Kingdom (P.P.P.); and Cardiovascular Research Center and Department of Physiology, Temple University School of Medicine, Philadelphia, PA (S.R.H.).
Steven R HouserFrom Department of Cardiovascular Sciences, National Heart and Lung Institute, Imperial College London, United Kingdom (A.V.G., M.B., J.L.S.-A., Z.I., A.A.-L., N.B., I.D., S.S., M.B.S., A.B., P.P.P., J.G.); University of Verona, School of Medicine, Verona, Italy (M.B., G.F.); Department of Cardiothoracic Surgery, Hammersmith Hospital, National Heart and Lung Institute, Imperial College London, United Kingdom (P.P.P.); and Cardiovascular Research Center and Department of Physiology, Temple University School of Medicine, Philadelphia, PA (S.R.H.).
Julia GorelikFrom Department of Cardiovascular Sciences, National Heart and Lung Institute, Imperial College London, United Kingdom (A.V.G., M.B., J.L.S.-A., Z.I., A.A.-L., N.B., I.D., S.S., M.B.S., A.B., P.P.P., J.G.); University of Verona, School of Medicine, Verona, Italy (M.B., G.F.); Department of Cardiothoracic Surgery, Hammersmith Hospital, National Heart and Lung Institute, Imperial College London, United Kingdom (P.P.P.); and Cardiovascular Research Center and Department of Physiology, Temple University School of Medicine, Philadelphia, PA (S.R.H.). j.gorelik@ic.ac.uk.
Hammersmith Hospital · GBUniversity of Verona · ITImperial College London · GB

Funding

Targeted Cancer Therapeutics and Heart Failure: Mechanisms and Post-injury RepairP01HL091799 · NHLBI · THOMAS JEFFERSON UNIVERSITY · PI KOCH, WALTER J. · 2008 to 2018
$23.1M
TRPC Channel Regulation of Cardiac Hypertrophy and ContractilityR01HL119229 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI HOUSER, STEVEN R · 2014 to 2017
$1.1M
British Heart Foundation 12/18/30088British Heart Foundation RG/12/18/30088NHLBI NIH HHS P01 HL091799NHLBI NIH HHS R01 HL119229Wellcome Trust 090594
6 · The paper itself

Abstract

backgroundDistinct subpopulations of L-type calcium channels (LTCCs) with different functional properties exist in cardiomyocytes. Disruption of cellular structure may affect LTCC in a microdomain-specific manner and contribute to the pathophysiology of cardiac diseases, especially in cells lacking organized transverse tubules (T-tubules) such as atrial myocytes (AMs). METHODS AND

resultsIsolated rat and human AMs were characterized by scanning ion conductance, confocal, and electron microscopy. Half of AMs possessed T-tubules and structured topography, proportional to cell width. A bigger proportion of myocytes in the left atrium had organized T-tubules and topography than in the right atrium. Super-resolution scanning patch clamp showed that LTCCs distribute equally in T-tubules and crest areas of the sarcolemma, whereas, in ventricular myocytes, LTCCs primarily cluster in T-tubules. Rat, but not human, T-tubule LTCCs had open probability similar to crest LTCCs, but exhibited ≈ 40% greater current. Optical mapping of Ca(2+) transients revealed that rat AMs presented ≈ 3-fold as many spontaneous Ca(2+) release events as ventricular myocytes. Occurrence of crest LTCCs and spontaneous Ca(2+) transients were eliminated by either a caveolae-targeted LTCC antagonist or disrupting caveolae with methyl-β-cyclodextrin, with an associated ≈ 30% whole-cell ICa,L reduction. Heart failure (16 weeks post-myocardial infarction) in rats resulted in a T-tubule degradation (by ≈ 40%) and significant elevation of spontaneous Ca(2+) release events. Although heart failure did not affect LTCC occurrence, it led to ≈ 25% decrease in T-tubule LTCC amplitude.

conclusionsWe provide the first direct evidence for the existence of 2 distinct subpopulations of functional LTCCs in rat and human AMs, with their biophysical properties modulated in heart failure in a microdomain-specific manner.

Indexed as

Heart AtriaAnimalsCalcium Channels, L-TypeCalcium SignalingHumansMembrane MicrodomainsMyocytes, CardiacRatsSpecies SpecificityCalcium Channels, L-Typecalcium channelsheart atriaheart failuremyocytes, cardiacscanning ion conductance microscopyT-tubules

Identifiers

PMID26450916
PMCPMC4689179
OpenAlexW2221427990

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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.