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* Department of Physiology, Texas Tech University Health Sciences Center, Lubbock, Texas; and Department of Medicine, Krannert Institute of Cardiology, Indianapolis, Indiana
Correspondence: Address reprint requests to Dr. Sandor Györke, Dept. of Physiology, Texas Tech University Health Sciences Center, 3601 4th St., STOP 6551, Lubbock, TX 79430-6551. Fax: 806-743-1512; E-mail: sandor.gyorke{at}ttuhsc.edu.
The level of Ca inside the sarcoplasmic reticulum (SR) is an important determinant of functional activity of the Ca release channel/ryanodine receptor (RyR) in cardiac muscle. However, the molecular basis of RyR regulation by luminal Ca remains largely unknown. In the present study, we investigated the potential role of the cardiac SR luminal auxiliary proteins calsequestrin (CSQ), triadin 1, and junctin in forming the luminal calcium sensor for the cardiac RyR. Recordings of single RyR channels incorporated into lipid bilayers, from either SR vesicle or purified RyR preparations, were performed in the presence of MgATP using Cs+ as the charge carrier. Raising luminal [Ca] from 20 µM to 5 mM increased the open channel probability (Po) of native RyRs in SR vesicles, but not of purified RyRs. Adding CSQ to the luminal side of the purified channels produced no significant changes in Po, nor did it restore the ability of RyRs to respond to luminal Ca. When triadin 1 and junctin were added to the luminal side of purified channels, RyR Po increased significantly; however, the channels still remained unresponsive to changes in luminal [Ca]. In RyRs reassociated with triadin 1 and junctin, adding luminal CSQ produced a significant decrease in activity. After reassociation with all three proteins, RyRs responded to rises of luminal [Ca] by increasing their Po. These results suggest that a complex of CSQ, triadin 1, and junctin confer RyR luminal Ca sensitivity. CSQ apparently serves as a luminal Ca sensor that inhibits the channel at low luminal [Ca], whereas triadin 1 and/or junctin may be required to mediate interactions of CSQ with RyR.
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K. R. Sipido and D. Eisner Something old, something new: Changing views on the cellular mechanisms of heart failure Cardiovasc Res, November 1, 2005; 68(2): 167 - 174. [Full Text] [PDF]
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Z. Kubalova, D. Terentyev, S. Viatchenko-Karpinski, Y. Nishijima, I. Gyorke, R. Terentyeva, D. N. Q. da Cunha, A. Sridhar, D. S. Feldman, R. L. Hamlin, et al. Abnormal intrastore calcium signaling in chronic heart failure PNAS, September 27, 2005; 102(39): 14104 - 14109. [Abstract] [Full Text] [PDF]
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S. L.W. Miller, S. Currie, C. M. Loughrey, S. Kettlewell, T. Seidler, D. F. Reynolds, G. Hasenfuss, and G. L. Smith Effects of calsequestrin over-expression on excitation-contraction coupling in isolated rabbit cardiomyocytes Cardiovasc Res, September 1, 2005; 67(4): 667 - 677. [Abstract] [Full Text] [PDF]
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N. Lindegger and E. Niggli Paradoxical SR Ca2+ release in guinea-pig cardiac myocytes after {beta}-adrenergic stimulation revealed by two-photon photolysis of caged Ca2+ J. Physiol., June 15, 2005; 565(3): 801 - 813. [Abstract] [Full Text] [PDF]
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H. A. Charlier Jr., R. D. Olson, C. M. Thornock, W. K. Mercer, D. R. Olson, T. S. Broyles, D. J. Muhlestein, C. L. Larson, B. J. Cusack, and S. E. Shadle Investigations of Calsequestrin as a Target for Anthracyclines: Comparison of Functional Effects of Daunorubicin, Daunorubicinol, and Trifluoperazine Mol. Pharmacol., May 1, 2005; 67(5): 1505 - 1512. [Abstract] [Full Text] [PDF]
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N. A. Beard, M. G. Casarotto, L. Wei, M. Varsanyi, D. R. Laver, and A. F. Dulhunty Regulation of Ryanodine Receptors by Calsequestrin: Effect of High Luminal Ca2+ and Phosphorylation Biophys. J., May 1, 2005; 88(5): 3444 - 3454. [Abstract] [Full Text] [PDF]
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 P. Tavi, A. Hansson, S.-J. Zhang, N.-G. Larsson, and H. Westerblad Abnormal Ca2+ release and catecholamine-induced arrhythmias in mitochondrial cardiomyopathy Hum. Mol. Genet., April 15, 2005; 14(8): 1069 - 1076. [Abstract] [Full Text] [PDF]
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M. Morad, L. Cleemann, and B. C. Knollmann Triadin: The New Player on Excitation-Contraction Coupling Block Circ. Res., April 1, 2005; 96(6): 607 - 609. [Full Text] [PDF]
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D. Terentyev, S. E. Cala, T. D. Houle, S. Viatchenko-Karpinski, I. Gyorke, R. Terentyeva, S. C. Williams, and S. Gyorke Triadin Overexpression Stimulates Excitation-Contraction Coupling and Increases Predisposition to Cellular Arrhythmia in Cardiac Myocytes Circ. Res., April 1, 2005; 96(6): 651 - 658. [Abstract] [Full Text] [PDF]
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T. R. Shannon, F. Wang, J. Puglisi, C. Weber, and D. M. Bers A Mathematical Treatment of Integrated Ca Dynamics within the Ventricular Myocyte Biophys. J., November 1, 2004; 87(5): 3351 - 3371. [Abstract] [Full Text] [PDF]
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P. Szentesi, C. Pignier, M. Egger, E. G. Kranias, and E. Niggli Sarcoplasmic Reticulum Ca2+ Refilling Controls Recovery From Ca2+-Induced Ca2+ Release Refractoriness in Heart Muscle Circ. Res., October 15, 2004; 95(8): 807 - 813. [Abstract] [Full Text] [PDF]
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J. Zhou, B. S. Launikonis, E. Rios, and G. Brum Regulation of Ca2+ Sparks by Ca2+ and Mg2+ in Mammalian and Amphibian Muscle. An RyR Isoform-specific Role in Excitation-Contraction Coupling? J. Gen. Physiol., September 27, 2004; 124(4): 409 - 428. [Abstract] [Full Text] [PDF]
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