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Biophysical Reviews

, Volume 10, Issue 4, pp 1087–1095 | Cite as

Regulation of the RyR channel gating by Ca2+ and Mg2+

  • Derek R. Laver
Review

Abstract

Ryanodine receptors (RyRs) are the Ca2+ release channels in the sarcoplasmic reticulum in striated muscle which play an important role in excitation-contraction coupling and cardiac pacemaking. Single channel recordings have revealed a wealth of information about ligand regulation of RyRs from mammalian skeletal and cardiac muscle (RyR1 and RyR2, respectively). RyR subunit has a Ca2+ activation site located in the luminal and cytoplasmic domains of the RyR. These sites synergistically feed into a common gating mechanism for channel activation by luminal and cytoplasmic Ca2+. RyRs also possess two inhibitory sites in their cytoplasmic domains with Ca2+ affinities of the order of 1 μM and 1 mM. Magnesium competes with Ca2+ at these sites to inhibit RyRs and this plays an important role in modulating their Ca2+-dependent activity in muscle. This review focuses on how these sites lead to RyR modulation by Ca2+ and Mg2+ and how these mechanisms control Ca2+ release in excitation-contraction coupling and cardiac pacemaking.

Keywords

Ryanodine receptor RyR1 RyR2 Excitation-contraction coupling Cardiac pacemaking Ca2+ activation Mg2+ inhibition Ca2+ release channels 

Notes

Acknowledgments

Thanks to Dirk van Helden for suggesting the ‘Tipping Urn’ analogy in Fig. 2 and to Oliver Clarke for locating amino acids on the RyR1 structure in Fig. 1.

Funding

This work was supported by an infrastructure grant from NSW Health through Hunter Medical Research Institute.

Compliance with ethical standards

Conflict of interest

Derek R. Laver declares that he has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by the author.

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Copyright information

© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of Biomedical Sciences and PharmacyUniversity of Newcastle and Hunter Medical Research InstituteCallaghanAustralia

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