Evidence map›Paper›PMID 25740838›Full record

ArticleCirculation. Heart failure2015

Phosphoregulation of Cardiac Inotropy via Myosin Binding Protein-C During Increased Pacing Frequency or β1-Adrenergic Stimulation.

Carl W Tong, Xin Wu, Yang Liu, Paola C Rosas, Sakthivel Sadayappan, Andy Hudmon, Mariappan Muthuchamy, Patricia A Powers, Héctor H Valdivia, Richard L Moss

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

Article in Circulation. Heart failure, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
3.8field-weighted citation impact, top 6% 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

34 citing papers in PubMed, 48 citations in OpenAlex.

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  17. Review
  18. cGMP Signaling and Modulation in Heart Failure.Journal of cardiovascular pharmacology · 2020
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 1 country.

Carl W TongFrom the Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison (C.W.T., P.A.P., R.L.M.); Department of Medical Physiology (C.W.T., Y.L., P.C.R., M.M.) and Neuroscience and Experimental Therapeutics (X.W.), Texas A&M University Health Science Center College of Medicine, Temple; Baylor Scott & White Health, Temple, TX (C.W.T.); Department of Physiology, Loyola University Chicago Stritch School of Medicine, IL (S.S.); Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis (A.H.); and Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor (H.H.V.).
Xin WuFrom the Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison (C.W.T., P.A.P., R.L.M.); Department of Medical Physiology (C.W.T., Y.L., P.C.R., M.M.) and Neuroscience and Experimental Therapeutics (X.W.), Texas A&M University Health Science Center College of Medicine, Temple; Baylor Scott & White Health, Temple, TX (C.W.T.); Department of Physiology, Loyola University Chicago Stritch School of Medicine, IL (S.S.); Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis (A.H.); and Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor (H.H.V.).
Yang LiuFrom the Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison (C.W.T., P.A.P., R.L.M.); Department of Medical Physiology (C.W.T., Y.L., P.C.R., M.M.) and Neuroscience and Experimental Therapeutics (X.W.), Texas A&M University Health Science Center College of Medicine, Temple; Baylor Scott & White Health, Temple, TX (C.W.T.); Department of Physiology, Loyola University Chicago Stritch School of Medicine, IL (S.S.); Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis (A.H.); and Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor (H.H.V.).
Paola C RosasFrom the Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison (C.W.T., P.A.P., R.L.M.); Department of Medical Physiology (C.W.T., Y.L., P.C.R., M.M.) and Neuroscience and Experimental Therapeutics (X.W.), Texas A&M University Health Science Center College of Medicine, Temple; Baylor Scott & White Health, Temple, TX (C.W.T.); Department of Physiology, Loyola University Chicago Stritch School of Medicine, IL (S.S.); Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis (A.H.); and Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor (H.H.V.).
Sakthivel SadayappanFrom the Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison (C.W.T., P.A.P., R.L.M.); Department of Medical Physiology (C.W.T., Y.L., P.C.R., M.M.) and Neuroscience and Experimental Therapeutics (X.W.), Texas A&M University Health Science Center College of Medicine, Temple; Baylor Scott & White Health, Temple, TX (C.W.T.); Department of Physiology, Loyola University Chicago Stritch School of Medicine, IL (S.S.); Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis (A.H.); and Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor (H.H.V.).
Andy HudmonFrom the Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison (C.W.T., P.A.P., R.L.M.); Department of Medical Physiology (C.W.T., Y.L., P.C.R., M.M.) and Neuroscience and Experimental Therapeutics (X.W.), Texas A&M University Health Science Center College of Medicine, Temple; Baylor Scott & White Health, Temple, TX (C.W.T.); Department of Physiology, Loyola University Chicago Stritch School of Medicine, IL (S.S.); Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis (A.H.); and Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor (H.H.V.).
Mariappan MuthuchamyFrom the Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison (C.W.T., P.A.P., R.L.M.); Department of Medical Physiology (C.W.T., Y.L., P.C.R., M.M.) and Neuroscience and Experimental Therapeutics (X.W.), Texas A&M University Health Science Center College of Medicine, Temple; Baylor Scott & White Health, Temple, TX (C.W.T.); Department of Physiology, Loyola University Chicago Stritch School of Medicine, IL (S.S.); Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis (A.H.); and Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor (H.H.V.).
Patricia A PowersFrom the Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison (C.W.T., P.A.P., R.L.M.); Department of Medical Physiology (C.W.T., Y.L., P.C.R., M.M.) and Neuroscience and Experimental Therapeutics (X.W.), Texas A&M University Health Science Center College of Medicine, Temple; Baylor Scott & White Health, Temple, TX (C.W.T.); Department of Physiology, Loyola University Chicago Stritch School of Medicine, IL (S.S.); Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis (A.H.); and Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor (H.H.V.).
Héctor H ValdiviaFrom the Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison (C.W.T., P.A.P., R.L.M.); Department of Medical Physiology (C.W.T., Y.L., P.C.R., M.M.) and Neuroscience and Experimental Therapeutics (X.W.), Texas A&M University Health Science Center College of Medicine, Temple; Baylor Scott & White Health, Temple, TX (C.W.T.); Department of Physiology, Loyola University Chicago Stritch School of Medicine, IL (S.S.); Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis (A.H.); and Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor (H.H.V.).
Richard L MossFrom the Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison (C.W.T., P.A.P., R.L.M.); Department of Medical Physiology (C.W.T., Y.L., P.C.R., M.M.) and Neuroscience and Experimental Therapeutics (X.W.), Texas A&M University Health Science Center College of Medicine, Temple; Baylor Scott & White Health, Temple, TX (C.W.T.); Department of Physiology, Loyola University Chicago Stritch School of Medicine, IL (S.S.); Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis (A.H.); and Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor (H.H.V.). rlmoss@wisc.edu.
Indiana University – Purdue University Indianapolis · USLoyola University Chicago · USIndiana University School of MedicineBaylor Scott & White Health · US

Funding

RYANODINE RECEPTORS, Ca2+-TRIGGERED ARRHYTHMIAS AND HCMP01HL094291 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI MOSS, RICHARD L · 2009 to 2013
$9.7M
Ryanodine Receptors, Calcium-dependent Arrhythmias & HCMR01HL055438 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI VALDIVIA, HECTOR H · 1996 to 2023
$8.0M
My-BP-C Modulation of Cardiac ContractionR37HL082900 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI MOSS, RICHARD L · 2006 to 2015
$6.0M
Cytosolic Calcium Sweeper in Cardiac MyocytesR01HL120108 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI VALDIVIA, HECTOR H · 2014 to 2017
$1.5M
Contributions of Cardiac Myosin Binding Protein-C to Healthy and Failing HeartsK08HL114877 · NHLBI · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI TONG, CARL WEI-CHAN · 2012 to 2016
$656k
NHLBI NIH HHS K08 HL114877NHLBI NIH HHS K08HL114877NHLBI NIH HHS P01 HL094291NHLBI NIH HHS R01 HL055438NHLBI NIH HHS R01 HL120108NHLBI NIH HHS R37 HL082900PHS HHS R37-82900
6 · The paper itself

Abstract

backgroundMammalian hearts exhibit positive inotropic responses to β-adrenergic stimulation as a consequence of protein kinase A-mediated phosphorylation or as a result of increased beat frequency (the Bowditch effect). Several membrane and myofibrillar proteins are phosphorylated under these conditions, but the relative contributions of these to increased contractility are not known. Phosphorylation of cardiac myosin-binding protein-C (cMyBP-C) by protein kinase A accelerates the kinetics of force development in permeabilized heart muscle, but its role in vivo is unknown. Such understanding is important because adrenergic responsiveness of the heart and the Bowditch effect are both depressed in heart failure. METHODS AND

resultsThe roles of cMyBP-C phosphorylation were studied using mice in which either WT or nonphosphorylatable forms of cMyBP-C [ser273ala, ser282ala, ser302ala: cMyBP-C(t3SA)] were expressed at similar levels on a cMyBP-C null background. Force and [Ca(2+)]in measurements in isolated papillary muscles showed that the increased force and twitch kinetics because increased pacing or β1-adrenergic stimulation were nearly absent in cMyBP-C(t3SA) myocardium, even though [Ca(2+)]in transients under each condition were similar to WT. Biochemical measurements confirmed that protein kinase A phosphorylated ser273, ser282, and ser302 in WT cMyBP-C. In contrast, CaMKIIδ, which is activated by increased pacing, phosphorylated ser302 principally, ser282 to a lesser degree, and ser273 not at all.

conclusionsPhosphorylation of cMyBP-C increases the force and kinetics of twitches in living cardiac muscle. Further, cMyBP-C is a principal mediator of increased contractility observed with β-adrenergic stimulation or increased pacing because of protein kinase A and CaMKIIδ phosphorylations of cMyB-C.

Indexed as

Cardiac Pacing, ArtificialAdrenergic beta-1 Receptor AgonistsAnimalsCalcium-Calmodulin-Dependent Protein Kinase Type 2Calcium SignalingCardiotonic AgentsCarrier ProteinsCyclic AMP-Dependent Protein KinasesEnzyme ActivationGenotypeKineticsMice, TransgenicMuscle StrengthMutationMyocardial ContractionMyosin Binding Protein CAdrenergic beta-1 Receptor AgonistsCalcium-Calmodulin-Dependent Protein Kinase Type 2Camk2d protein, mouseCardiotonic AgentsCarrier ProteinsCyclic AMP-Dependent Protein KinasesMyosin Binding Protein Ccontractilitymyosin-binding protein-Cphosphorylation

Identifiers

PMID25740838
PMCPMC4439328
OpenAlexW2143515941

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.