Giant ankyrin-G regulates cardiac function.

Animals Animals, Newborn Female Heart / physiology Male Mice Mice, Knockout Myocytes, Cardiac / cytology Neurons / cytology Phosphate Transport Proteins / physiology
Nav1.5 animal model ankyrin-G arrhythmia cardiovascular disease cytoskeleton giant ankyrin-G myocytes

Journal

The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R

Informations de publication

Date de publication:
Historique:
received: 06 10 2020
revised: 01 03 2021
accepted: 02 03 2021
pubmed: 7 3 2021
medline: 21 8 2021
entrez: 6 3 2021
Statut: ppublish

Résumé

Cardiovascular disease (CVD) remains the most common cause of adult morbidity and mortality in developed nations. As a result, predisposition for CVD is increasingly important to understand. Ankyrins are intracellular proteins required for the maintenance of membrane domains. Canonical ankyrin-G (AnkG) has been shown to be vital for normal cardiac function, specifically cardiac excitability, via targeting and regulation of the cardiac voltage-gated sodium channel. Noncanonical (giant) AnkG isoforms play a key role in neuronal membrane biogenesis and excitability, with evidence for human neurologic disease when aberrant. However, the role of giant AnkG in cardiovascular tissue has yet to be explored. Here, we identify giant AnkG in the myocardium and identify that it is enriched in 1-week-old mice. Using a new mouse model lacking giant AnkG expression in myocytes, we identify that young mice displayed a dilated cardiomyopathy phenotype with aberrant electrical conduction and enhanced arrhythmogenicity. Structural and electrical dysfunction occurred at 1 week of age, when giant AnkG was highly expressed and did not appreciably change in adulthood until advanced age. At a cellular level, loss of giant AnkG results in delayed and early afterdepolarizations. However, surprisingly, giant AnkG cKO myocytes display normal I

Identifiants

DOI: 10.1016/j.jbc.2021.100507 PMID: 33675749 PMC: PMC8040283
pubmed: 33675749
pii: S0021-9258(21)00283-0
doi: 10.1016/j.jbc.2021.100507
pmc: PMC8040283
pii:
doi:

Substances chimiques

Ankh protein, mouse 0
Phosphate Transport Proteins 0

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

100507

Subventions

Organisme : NHLBI NIH HHS
ID : R35 HL135754
Pays : United States
Organisme : NHLBI NIH HHS
ID : R00 HL146969
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL148701
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL139348
Pays : United States
Organisme : NHLBI NIH HHS
ID : K99 HL146969
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL135096
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL134824
Pays : United States

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.

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Auteurs

Omer Cavus (O)

Department of Physiology and Cell Biology, The Ohio State University, Columbus, Ohio, USA; The Frick Center for Heart Failure and Arrhythmia, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.

Jordan Williams (J)

Department of Physiology and Cell Biology, The Ohio State University, Columbus, Ohio, USA; The Frick Center for Heart Failure and Arrhythmia, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.

Hassan Musa (H)

Department of Physiology and Cell Biology, The Ohio State University, Columbus, Ohio, USA; The Frick Center for Heart Failure and Arrhythmia, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.

Mona El Refaey (M)

Department of Physiology and Cell Biology, The Ohio State University, Columbus, Ohio, USA; The Frick Center for Heart Failure and Arrhythmia, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.

Dan Gratz (D)

The Frick Center for Heart Failure and Arrhythmia, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA; Department of Biomedical Engineering, College of Engineering, The Ohio State University, Columbus, Ohio, USA.

Rebecca Shaheen (R)

The Frick Center for Heart Failure and Arrhythmia, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA; Department of Biomedical Engineering, College of Engineering, The Ohio State University, Columbus, Ohio, USA.

Neill A Schwieterman (NA)

Department of Physiology and Cell Biology, The Ohio State University, Columbus, Ohio, USA; The Frick Center for Heart Failure and Arrhythmia, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.

Sara Koenig (S)

Department of Physiology and Cell Biology, The Ohio State University, Columbus, Ohio, USA; The Frick Center for Heart Failure and Arrhythmia, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.

Steve Antwi-Boasiako (S)

The Frick Center for Heart Failure and Arrhythmia, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.

Lindsay J Young (LJ)

Department of Physiology and Cell Biology, The Ohio State University, Columbus, Ohio, USA; The Frick Center for Heart Failure and Arrhythmia, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.

Xianyao Xu (X)

Department of Physiology and Cell Biology, The Ohio State University, Columbus, Ohio, USA; The Frick Center for Heart Failure and Arrhythmia, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.

Mei Han (M)

Department of Physiology and Cell Biology, The Ohio State University, Columbus, Ohio, USA; The Frick Center for Heart Failure and Arrhythmia, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.

Loren E Wold (LE)

Department of Physiology and Cell Biology, The Ohio State University, Columbus, Ohio, USA; The Frick Center for Heart Failure and Arrhythmia, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.

Thomas J Hund (TJ)

The Frick Center for Heart Failure and Arrhythmia, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA; Department of Biomedical Engineering, College of Engineering, The Ohio State University, Columbus, Ohio, USA; Department of Internal Medicine/Division of Cardiovascular Medicine, The Ohio State University, Columbus, Ohio, USA.

Peter J Mohler (PJ)

Department of Physiology and Cell Biology, The Ohio State University, Columbus, Ohio, USA; The Frick Center for Heart Failure and Arrhythmia, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA; Department of Internal Medicine/Division of Cardiovascular Medicine, The Ohio State University, Columbus, Ohio, USA.

Elisa A Bradley (EA)

The Frick Center for Heart Failure and Arrhythmia, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA; Department of Internal Medicine/Division of Cardiovascular Medicine, The Ohio State University, Columbus, Ohio, USA. Electronic address: elisa.bradley@osumc.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Giant ankyrin-G regulates cardiac function.
questionsmedicales.fr › Eucaryotes › Animaux › Groupes animaux › Animaux nouveau-nés › Giant ankyrin-G regulates cardiac function.
questionsmedicales.fr › Système cardiovasculaire › Coeur › Giant ankyrin-G regulates cardiac function.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Giant ankyrin-G regulates cardiac function.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › Giant ankyrin-G regulates cardiac function.
questionsmedicales.fr › Cellules › Cellules musculaires › Myocytes cardiaques › Giant ankyrin-G regulates cardiac function.
questionsmedicales.fr › Cellules › Neurones › Giant ankyrin-G regulates cardiac function.
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Pompes ioniques › Transporteurs d'anions › Protéines de transport du phosphate › Giant ankyrin-G regulates cardiac function.