Functional interaction between calsequestrin and ryanodine receptor in the heart
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Cellular and Molecular Life Sciences
REVIEW
Functional interaction between calsequestrin and ryanodine receptor in the heart Marta Gaburjakova • Naresh C. Bal • Jana Gaburjakova • Muthu Periasamy
Received: 29 June 2012 / Revised: 2 October 2012 / Accepted: 15 October 2012 / Published online: 30 October 2012 Ó Springer Basel 2012
Abstract Evidence obtained in the last two decades indicates that calsequestrin (CSQ2), as the major Ca2?binding protein in the sarcoplasmic reticulum of cardiac myocytes, communicates changes in the luminal Ca2? concentration to the cardiac ryanodine receptor (RYR2) channel. This review summarizes the major aspects in the interaction between CSQ2 and the RYR2 channel. The single channel properties of RYR2 channels, discussed here in the context of structural changes in CSQ2 after Ca2? binding, are particularly important. We focus on five important questions concerning: (1) the method for reliable detection of CSQ2 on the reconstituted RYR2 channel complex; (2) the power of the procedure to strip CSQ2 from the RYR2 channel complex; (3) structural changes in CSQ2 upon binding of Ca2? which cause CSQ2 dissociation; (4) the potential role of CSQ2-independent regulation of the RYR2 activity by luminal Ca2?; and (5) the vizualization of CSQ2 dissociation from the RYR2 channel complex on the single channel level. We discuss the potential sources of the conflicting experimental results which may aid detailed understanding of the CSQ2 regulatory role. Although we mainly focus on the cardiac
M. Gaburjakova and N. C. Bal contributed equally to this work. M. Gaburjakova (&) J. Gaburjakova Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Vlarska 5, 833 34 Bratislava, Slovak Republic e-mail: [email protected] N. C. Bal M. Periasamy Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, OH 43210, USA
isoform of the proteins, some aspects of more extensive work carried out on the skeletal isoform are also discussed. Keywords Cardiac muscle Ryanodine receptor Luminal Ca2? Calsequestrin Planar lipid membrane
Introduction The cardiac ryanodine receptor (RYR2) channel plays a key role in excitation–contraction (EC) coupling in the heart, providing the pathway for release of Ca2? from the sarcoplasmic reticulum (SR) required for activation of cardiac contraction. It is becoming increasingly evident that the Ca2? release by RYR2 channels is governed not only by cytosolic Ca2? but also by Ca2? in the lumen of the SR (luminal Ca2?). The first evidence of a regulatory role of luminal Ca2? was reported by Fabiato and Fabiato [1, 2]. They showed that the magnitude of Ca2? release was scaled by the Ca2? loading of the SR. These findings are easily explained by an increase in the Ca2? gradient across the SR membrane; and thus, increased amplitude in the Ca2? current. However, studies on muscle cells and isolated vesicles have revealed that the rate of Ca2? release was increased by luminal Ca2? too steeply (non-linearly)
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