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Mechanisms of SR calcium release in healthy and failing human hearts

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Abstract

Normal heart contraction and rhythm relies on the proper flow of calcium ions (Ca2+) into cardiac cells and between their intracellular organelles, and any disruption can lead to arrhythmia and sudden cardiac death. Electrical excitation of the surface membrane activates voltage-dependent L-type Ca2+ channels to open and allow Ca2+ to enter the cytoplasm. The subsequent increase in cytoplasmic Ca2+ concentration activates calcium release channels (RyR2) located at specialised Ca2+ release sites in the sarcoplasmic reticulum (SR), which serves as an intracellular Ca2+ store. Animal models have provided valuable insights into how intracellular Ca2+ transport mechanisms are altered in human heart failure. The aim of this review is to examine how Ca2+ release sites are remodelled in heart failure and how this affects intracellular Ca2+ transport with an emphasis on Ca2+ release mechanisms in the SR. Current knowledge on how heart failure alters the regulation of RyR2 by Ca2+ and Mg2+ and how these mechanisms control the activity of RyR2 in the confines of the Ca2+ release sites is reviewed.

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Acknowledgements

This work was supported by a scholarship from the University of Newcastle and the Hunter Medical Research Institute and a project grant from the NH&MRC (631052).

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Kafa Walweel declares that she has no conflict of interest Derek R. Laver declares that he has no conflict of intrest.

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This article does not contain any studies with human or animal subjects performed by the any of the authors.

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Authors and Affiliations

  1. School of Biomedical Sciences and Pharmacy, University of Newcastle and Hunter Medical Research Institute, Callaghan, NSW, 2308, Australia

    K. Walweel & D. R. Laver

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  1. K. Walweel
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  2. D. R. Laver
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Correspondence to D. R. Laver.

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Special Issue: Biophysics of Human Heart Failure

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Walweel, K., Laver, D.R. Mechanisms of SR calcium release in healthy and failing human hearts. Biophys Rev 7, 33–41 (2015). https://doi.org/10.1007/s12551-014-0152-4

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  • DOI: https://doi.org/10.1007/s12551-014-0152-4

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