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Mechanisms underlying pathological Ca2+ handling in diseases of the heart

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A Correction to this article was published on 20 January 2021

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Abstract

Cardiomyocyte contraction relies on precisely regulated intracellular Ca2+ signaling through various Ca2+ channels and transporters. In this article, we will review the physiological regulation of Ca2+ handling and its role in maintaining normal cardiac rhythm and contractility. We discuss how inherited variants or acquired defects in Ca2+ channel subunits contribute to the development or progression of diseases of the heart. Moreover, we highlight recent insights into the role of protein phosphatase subunits and striated muscle preferentially expressed protein kinase (SPEG) in atrial fibrillation, heart failure, and cardiomyopathies. Finally, this review summarizes current drug therapies and new advances in genome editing as therapeutic strategies for the cardiac diseases caused by aberrant intracellular Ca2+ signaling.

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Abbreviations

AC:

Arrhythmogenic cardiomyopathy

AF:

Atrial fibrillation

CaM:

Calmodulin

CASQ3:

Calsequestrin-2

CICR:

Ca2+-induced Ca2+ release

CPVT:

Catecholaminergic polymorphic ventricular tachycardia

DCM:

Dilated cardiomyopathy

EC:

Excitation-coupling

FKBP12.6:

FK506-binding protein-12.6

HCM:

Hypertrophic cardiomyopathy

HF:

Heart failure

JMC:

Junctional membrane complex

LQTS:

Long QT syndrome

LTCC:

L-type Ca2+ channel

NCX:

Na+/Ca2+ exchanger

RyR2:

Ryanodine receptor type-2

SPEG:

Striated muscle preferentially expressed protein kinase

SERCA2a:

Sarco/endoplasmic reticulum Ca2+-ATPase

SR:

Sarcoplasmic reticulum

SUMO-1:

Small ubiquitin-like modifier type-1

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Funding

XW was funded through NIH grants R01-HL089598, R01-HL091947, R01-HL117641, and R01-HL147108.

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  1. Satadru K. Lahiri and Yuriana Aguilar-Sanchez contributed equally to this work.

Authors and Affiliations

  1. Cardiovascular Research Institute, Baylor College of Medicine, One Baylor Plaza, BCM335, Houston, TX, 77030, USA

    Satadru K. Lahiri, Yuriana Aguilar-Sanchez & Xander H. T. Wehrens

  2. Department of Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, TX, 77030, USA

    Satadru K. Lahiri, Yuriana Aguilar-Sanchez & Xander H. T. Wehrens

  3. Department of Medicine, Baylor College of Medicine, Houston, TX, 77030, USA

    Xander H. T. Wehrens

  4. Department of Neuroscience, Baylor College of Medicine, Houston, TX, 77030, USA

    Xander H. T. Wehrens

  5. Department of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA

    Xander H. T. Wehrens

  6. Center for Space Medicine, Baylor College of Medicine, Houston, TX, 77030, USA

    Xander H. T. Wehrens

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SL, YAS, and XW collaborated in writing the review article.

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XHTW is a founding partner of Elex Biotech, a start-up company that developed drug molecules to target ryanodine receptors for treatment of cardiac arrhythmias. Other authors have no conflicts related to this study.

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The original online version of this article was revised: The original article was published with an error. Reference '95' was added in the text but was not added in the reference list. Therefore, current hyperlink on the in-text reference 95 shows wrong citation. This further changed the whole reference list from 95 to end and shows total of 201 reference instead of submitted 202 references.

Satadru K. Lahiri and Yuriana Aguilar-Sanchez shared first authorship

This article is part of the special issue on Calcium Signal Dynamics in Cardiac Myocytes and Fibroblasts: Mechanisms in Pflügers Archiv—European Journal of Physiology

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Lahiri, S.K., Aguilar-Sanchez, Y. & Wehrens, X.H.T. Mechanisms underlying pathological Ca2+ handling in diseases of the heart. Pflugers Arch - Eur J Physiol 473, 331–347 (2021). https://doi.org/10.1007/s00424-020-02504-z

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