Evidence map›Paper›PMID 26304511›Full record

ArticleCirculation. Arrhythmia and electrophysiology2015

Molecular Mapping of Sinoatrial Node HCN Channel Expression in the Human Heart.

Ning Li, Thomas A Csepe, Brian J Hansen, Halina Dobrzynski, Robert S D Higgins, Ahmet Kilic, Peter J Mohler, Paul M L Janssen, Michael R Rosen, Brandon J Biesiadecki and 1 more

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

Article in Circulation. Arrhythmia and electrophysiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 1 pooled it
5.9field-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

54 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Tissue elasticity modulates cardiac pacemaker cell automaticity.American journal of physiology. Heart and circulatory physiology · 2025
    Article
  5. Review
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  8. Review
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  10. Article
  11. A gain-of-function HCN4 mutant in the HCN domain is responsible for inappropriate sinus tachycardia in a Spanish family.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  12. Article
  13. Article
  14. Article
  15. Compartmentalized cAMP signalling and control of cardiac rhythm.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
    Review
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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

11 authors at 1 institution in 1 country.

Ning LiFrom the Department of Physiology & Cell Biology and Dorothy M. Davis Heart & Lung Research Institute (N.L., T.A.C., B.J.H., P.J.M., P.M.L.J., B.J.B., V.V.F.), Department of Surgery and Dorothy M. Davis Heart & Lung Research Institute (R.S.D.H., A.K.), The Ohio State University Wexner Medical Center, Columbus; Institute of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom (H.D.); and Departments of Pharmacology and Pediatrics, Columbia University, New York, NY (M.R.R.).
Thomas A CsepeFrom the Department of Physiology & Cell Biology and Dorothy M. Davis Heart & Lung Research Institute (N.L., T.A.C., B.J.H., P.J.M., P.M.L.J., B.J.B., V.V.F.), Department of Surgery and Dorothy M. Davis Heart & Lung Research Institute (R.S.D.H., A.K.), The Ohio State University Wexner Medical Center, Columbus; Institute of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom (H.D.); and Departments of Pharmacology and Pediatrics, Columbia University, New York, NY (M.R.R.).
Brian J HansenFrom the Department of Physiology & Cell Biology and Dorothy M. Davis Heart & Lung Research Institute (N.L., T.A.C., B.J.H., P.J.M., P.M.L.J., B.J.B., V.V.F.), Department of Surgery and Dorothy M. Davis Heart & Lung Research Institute (R.S.D.H., A.K.), The Ohio State University Wexner Medical Center, Columbus; Institute of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom (H.D.); and Departments of Pharmacology and Pediatrics, Columbia University, New York, NY (M.R.R.).
Halina DobrzynskiFrom the Department of Physiology & Cell Biology and Dorothy M. Davis Heart & Lung Research Institute (N.L., T.A.C., B.J.H., P.J.M., P.M.L.J., B.J.B., V.V.F.), Department of Surgery and Dorothy M. Davis Heart & Lung Research Institute (R.S.D.H., A.K.), The Ohio State University Wexner Medical Center, Columbus; Institute of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom (H.D.); and Departments of Pharmacology and Pediatrics, Columbia University, New York, NY (M.R.R.).
Robert S D HigginsFrom the Department of Physiology & Cell Biology and Dorothy M. Davis Heart & Lung Research Institute (N.L., T.A.C., B.J.H., P.J.M., P.M.L.J., B.J.B., V.V.F.), Department of Surgery and Dorothy M. Davis Heart & Lung Research Institute (R.S.D.H., A.K.), The Ohio State University Wexner Medical Center, Columbus; Institute of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom (H.D.); and Departments of Pharmacology and Pediatrics, Columbia University, New York, NY (M.R.R.).
Ahmet KilicFrom the Department of Physiology & Cell Biology and Dorothy M. Davis Heart & Lung Research Institute (N.L., T.A.C., B.J.H., P.J.M., P.M.L.J., B.J.B., V.V.F.), Department of Surgery and Dorothy M. Davis Heart & Lung Research Institute (R.S.D.H., A.K.), The Ohio State University Wexner Medical Center, Columbus; Institute of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom (H.D.); and Departments of Pharmacology and Pediatrics, Columbia University, New York, NY (M.R.R.).
Peter J MohlerFrom the Department of Physiology & Cell Biology and Dorothy M. Davis Heart & Lung Research Institute (N.L., T.A.C., B.J.H., P.J.M., P.M.L.J., B.J.B., V.V.F.), Department of Surgery and Dorothy M. Davis Heart & Lung Research Institute (R.S.D.H., A.K.), The Ohio State University Wexner Medical Center, Columbus; Institute of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom (H.D.); and Departments of Pharmacology and Pediatrics, Columbia University, New York, NY (M.R.R.).
Paul M L JanssenFrom the Department of Physiology & Cell Biology and Dorothy M. Davis Heart & Lung Research Institute (N.L., T.A.C., B.J.H., P.J.M., P.M.L.J., B.J.B., V.V.F.), Department of Surgery and Dorothy M. Davis Heart & Lung Research Institute (R.S.D.H., A.K.), The Ohio State University Wexner Medical Center, Columbus; Institute of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom (H.D.); and Departments of Pharmacology and Pediatrics, Columbia University, New York, NY (M.R.R.).
Michael R RosenFrom the Department of Physiology & Cell Biology and Dorothy M. Davis Heart & Lung Research Institute (N.L., T.A.C., B.J.H., P.J.M., P.M.L.J., B.J.B., V.V.F.), Department of Surgery and Dorothy M. Davis Heart & Lung Research Institute (R.S.D.H., A.K.), The Ohio State University Wexner Medical Center, Columbus; Institute of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom (H.D.); and Departments of Pharmacology and Pediatrics, Columbia University, New York, NY (M.R.R.).
Brandon J BiesiadeckiFrom the Department of Physiology & Cell Biology and Dorothy M. Davis Heart & Lung Research Institute (N.L., T.A.C., B.J.H., P.J.M., P.M.L.J., B.J.B., V.V.F.), Department of Surgery and Dorothy M. Davis Heart & Lung Research Institute (R.S.D.H., A.K.), The Ohio State University Wexner Medical Center, Columbus; Institute of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom (H.D.); and Departments of Pharmacology and Pediatrics, Columbia University, New York, NY (M.R.R.).
Vadim V FedorovFrom the Department of Physiology & Cell Biology and Dorothy M. Davis Heart & Lung Research Institute (N.L., T.A.C., B.J.H., P.J.M., P.M.L.J., B.J.B., V.V.F.), Department of Surgery and Dorothy M. Davis Heart & Lung Research Institute (R.S.D.H., A.K.), The Ohio State University Wexner Medical Center, Columbus; Institute of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom (H.D.); and Departments of Pharmacology and Pediatrics, Columbia University, New York, NY (M.R.R.). vadim.fedorov@osumc.edu fedorov.2@osu.edu.
University of Manchester · GB

Funding

Frequency-dependent modulation of cardiac myofilament function in health/diseaseR01HL113084 · NHLBI · OHIO STATE UNIVERSITY · PI JANSSEN, PAULUS ML · 2012 to 2023
$4.6M
Integration of structure and signaling in cardiac pacemaker functionR01HL115580 · NHLBI · OHIO STATE UNIVERSITY · PI FEDOROV, VADIM V · 2013 to 2021
$4.2M
Role of spectrin/ankyrin-G complex in myocyte signaling and cardiac excitabilityR01HL083422 · NHLBI · VANDERBILT UNIVERSITY · PI MOHLER, PETER J. · 2006 to 2016
$3.8M
Integrated Crosstalk of Thin Filament Post-translational ModificationsR01HL114940 · NHLBI · OHIO STATE UNIVERSITY · PI BIESIADECKI, BRANDON J · 2013 to 2021
$3.6M
Role of ankyrin-B in human arrhythmiaR01HL084583 · NHLBI · UNIVERSITY OF IOWA · PI MOHLER, PETER J. · 2006 to 2015
$3.4M
EHD proteins in cardiac membrane protein targeting and remodelingR01HL114383 · NHLBI · OHIO STATE UNIVERSITY · PI BOYDEN, PENELOPE ALTMAN, MOHLER, PETER J. · 2013 to 2016
$2.1M
NHLBI NIH HHS HL083422NHLBI NIH HHS HL084583NHLBI NIH HHS HL113084NHLBI NIH HHS HL114383NHLBI NIH HHS HL115580NHLBI NIH HHS R01 HL083422NHLBI NIH HHS R01 HL084583NHLBI NIH HHS R01 HL113084NHLBI NIH HHS R01 HL114383NHLBI NIH HHS R01 HL114940NHLBI NIH HHS R01 HL115580
6 · The paper itself

Abstract

backgroundThe hyperpolarization-activated current, If, plays an important role in sinoatrial node (SAN) pacemaking. Surprisingly, the distribution of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in human SAN has only been investigated at the mRNA level. Our aim was to define the expression pattern of HCN proteins in human SAN and different atrial regions. METHODS AND

resultsEntire SAN complexes were isolated from failing (n=5) and nonfailing (n=9) human hearts cardioplegically arrested in the operating room. Three-dimensional intramural SAN structure was identified as the fibrotic compact region around the SAN artery with Connexin 43-negative pacemaker cardiomyocytes visualized in Masson's trichrome and immunostained cryosections. SAN protein was precisely isolated from the adjacent frozen SAN tissue blocks using a 16G biopsy needle. The purity of the SAN protein was confirmed by Connexin 43 immunoblot. All 3 HCN isoform proteins were detected in SAN. HCN1 was predominantly distributed in the human SAN with a 125.1±40.2 (n=12) expression ratio of SAN to right atrium. HCN2 and HCN4 expression levels were higher in SAN than in atria, with SAN to right atrium ratios of 6.1±0.9 and 4.6±0.6 (n=12), respectively.

conclusionsThis is the first study to conduct precise 3D molecular mapping of the human SAN by isolating pure pacemaker SAN tissue. All 3 cardiac HCN isoforms had higher expression in the SAN than in the atria. HCN1 was almost exclusively expressed in SAN, emphasizing its utility as a new specific molecular marker of the human SAN and as a potential target of specific treatments intended to modify sinus rhythm.

Indexed as

AdultAgedFemaleHeart FailureHumansHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsImmunoblottingMaleMiddle AgedMuscle ProteinsMyocytes, CardiacPotassium ChannelsProtein IsoformsSinoatrial NodeHCN1 protein, humanHCN2 protein, humanHCN4 protein, humanHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsMuscle ProteinsPotassium ChannelsProtein IsoformsHCN pacemaker channelsheart failurehuman heartsinoatrial nodesinus node dysfunction

Identifiers

PMID26304511
PMCPMC4618238
OpenAlexW2106281384

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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.