Zinc controls RyR2 activity during excitation-contraction coupling

Alan J. Stewart; Samantha Jane Pitt

doi:10.1080/19336950.2015.1075784

Zinc controls RyR2 activity during excitation-contraction coupling

Research output: Contribution to journal › Article › peer-review

Abstract

Cardiac excitation-contraction (EC) coupling is a process which governs contractility of the heart through the controlled release of Ca²⁺ from the sarcoplasmic reticulum (SR). The type-2 ryanodine receptor (RyR2) is the route through which Ca²⁺ is released from the SR providing the necessary driving force for cellular contraction. In heart failure, RyR2-channels become
abnormally active, or ‘leaky’, and are unable to remain closed during diastole resulting in unwanted irregular contractile and electrical activity¹. Defective Zn²⁺ handling has been shown to contribute to the cellular pathology of certain cardiomyopathies which give rise to impaired contractility including heart failure ². This is likely a consequence of altered EC coupling as a result of modified RyR2 function. How zinc impacts upon the contractile force and the release
of calcium from intracellular stores in heart is not fully understood.

Original language	English
Pages (from-to)	223-225
Journal	Channels
Volume	9
Issue number	5
Early online date	28 Jul 2015
DOIs	https://doi.org/10.1080/19336950.2015.1075784
Publication status	Published - Sept 2015

Keywords

Ryanodine receptor
Excitation-contraction coupling
Ca2+-release
Zn2+-signalling
Cardiomyocyte

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10.1080/19336950.2015.1075784

stewart2015channels223
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.
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RSE/CRF Samantha Pitt Resrch Fellowship: Molecular mechanisms of NAADP-regulated signalling via Two Pore Channels
Pitt, S. J. (PI)
The Royal Society of Edinburgh
1/10/13 → 30/09/18
Project: Fellowship

Cite this

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title = "Zinc controls RyR2 activity during excitation-contraction coupling",

abstract = "Cardiac excitation-contraction (EC) coupling is a process which governs contractility of the heart through the controlled release of Ca2+ from the sarcoplasmic reticulum (SR). The type-2 ryanodine receptor (RyR2) is the route through which Ca2+ is released from the SR providing the necessary driving force for cellular contraction. In heart failure, RyR2-channels become abnormally active, or {\textquoteleft}leaky{\textquoteright}, and are unable to remain closed during diastole resulting in unwanted irregular contractile and electrical activity1. Defective Zn2+ handling has been shown to contribute to the cellular pathology of certain cardiomyopathies which give rise to impaired contractility including heart failure 2. This is likely a consequence of altered EC coupling as a result of modified RyR2 function. How zinc impacts upon the contractile force and the release of calcium from intracellular stores in heart is not fully understood.",

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AU - Pitt, Samantha Jane

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AB - Cardiac excitation-contraction (EC) coupling is a process which governs contractility of the heart through the controlled release of Ca2+ from the sarcoplasmic reticulum (SR). The type-2 ryanodine receptor (RyR2) is the route through which Ca2+ is released from the SR providing the necessary driving force for cellular contraction. In heart failure, RyR2-channels become abnormally active, or ‘leaky’, and are unable to remain closed during diastole resulting in unwanted irregular contractile and electrical activity1. Defective Zn2+ handling has been shown to contribute to the cellular pathology of certain cardiomyopathies which give rise to impaired contractility including heart failure 2. This is likely a consequence of altered EC coupling as a result of modified RyR2 function. How zinc impacts upon the contractile force and the release of calcium from intracellular stores in heart is not fully understood.

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KW - Excitation-contraction coupling

KW - Ca2+-release

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DO - 10.1080/19336950.2015.1075784

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Zinc controls RyR2 activity during excitation-contraction coupling

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Keywords

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Projects

RSE/CRF Samantha Pitt Resrch Fellowship: Molecular mechanisms of NAADP-regulated signalling via Two Pore Channels

Cite this