This Article Full Text Full Text (PDF) All Versions of this Article: 93/1/40    most recent 01.RES.0000079967.11815.19v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shannon, T. R. Articles by Bers, D. M. Search for Related Content PubMed PubMed Citation Articles by Shannon, T. R. Articles by Bers, D. M. Related Collections Structure Calcium cycling/excitation-contraction coupling Cell signalling/signal transduction Imaging Ion channels/membrane transport

(Circulation Research. 2003;93:40.)
© 2003 American Heart Association, Inc.

Cellular Biology

Ca²⁺ Scraps

Local Depletions of Free [Ca²⁺] in Cardiac Sarcoplasmic Reticulum During Contractions Leave Substantial Ca²⁺ Reserve

Thomas R. Shannon, Tao Guo, Donald M. Bers

From the Department of Physiology (T.R.S., T.G., D.M.B.), Loyola University Chicago, Maywood, Ill; Department of Molecular Biophysics and Physiology (T.R.S.), Rush University, Chicago, Ill.

Correspondence to Thomas R. Shannon, DVM, PhD, Department of Molecular Biophysics and Physiology, Rush University, 1750 W Harrison, Chicago, IL 60612. E-mail tshannon{at}rush.edu

Free [Ca²⁺] inside the sarcoplasmic reticulum ([Ca²⁺]_SR) is difficult to measure yet critically important in controlling many cellular systems. In cardiac myocytes, [Ca²⁺]_SR regulates cardiac contractility. We directly measure [Ca²⁺]_SR in intact cardiac myocytes dynamically and quantitatively during beats, with high spatial resolution. Diastolic [Ca²⁺]_SR (1 to 1.5 mmol/L) is only partially depleted (24% to 63%) during contraction. There is little temporal delay in the decline in [Ca²⁺]_SR at release junctions and between junctions, indicating rapid internal diffusion. The incomplete local Ca²⁺ release shows that the inherently positive feedback of Ca²⁺-induced Ca²⁺ release terminates, despite a large residual driving force. These findings place stringent novel constraints on how excitation-contraction coupling works in heart and also reveal a Ca²⁺ store reserve that could in principle be a therapeutic target to enhance cardiac function in heart failure.

Key Words: calcium homeostasis • sarcoplasmic reticulum • ryanodine receptors • confocal imaging • membrane transport

This article has been cited by other articles:

				T. L. Domeier, L. A. Blatter, and A. V. Zima Alteration of sarcoplasmic reticulum Ca2+ release termination by ryanodine receptor sensitization and in heart failure J. Physiol., November 1, 2009; 587(21): 5197 - 5209. [Abstract] [Full Text] [PDF]

				V. A. Maltsev and E. G. Lakatta Synergism of coupled subsarcolemmal Ca2+ clocks and sarcolemmal voltage clocks confers robust and flexible pacemaker function in a novel pacemaker cell model Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H594 - H615. [Abstract] [Full Text] [PDF]

				A. V. Zima, J. Qin, M. Fill, and L. A. Blatter Tricyclic antidepressant amitriptyline alters sarcoplasmic reticulum calcium handling in ventricular myocytes Am J Physiol Heart Circ Physiol, November 1, 2008; 295(5): H2008 - H2016. [Abstract] [Full Text] [PDF]

				A. V. Zima, E. Picht, D. M. Bers, and L. A. Blatter Termination of Cardiac Ca2+ Sparks: Role of Intra-SR [Ca2+], Release Flux, and Intra-SR Ca2+ Diffusion Circ. Res., October 10, 2008; 103(8): e105 - e115. [Abstract] [Full Text] [PDF]

				H. Cheng and W. J. Lederer Calcium Sparks Physiol Rev, October 1, 2008; 88(4): 1491 - 1545. [Abstract] [Full Text] [PDF]

				L. A. Venetucci, A. W. Trafford, S. C. O'Neill, and D. A. Eisner The sarcoplasmic reticulum and arrhythmogenic calcium release Cardiovasc Res, January 15, 2008; 77(2): 285 - 292. [Abstract] [Full Text] [PDF]

				S. Gyorke and D. Terentyev Modulation of ryanodine receptor by luminal calcium and accessory proteins in health and cardiac disease Cardiovasc Res, January 15, 2008; 77(2): 245 - 255. [Abstract] [Full Text] [PDF]

				A. V. Zima, D. J. Bare, G. A. Mignery, and L. A. Blatter IP3-dependent nuclear Ca2+ signalling in the mammalian heart J. Physiol., October 15, 2007; 584(2): 601 - 611. [Abstract] [Full Text] [PDF]

				T. Guo, X. Ai, T. R. Shannon, S. M. Pogwizd, and D. M. Bers Intra Sarcoplasmic Reticulum Free [Ca2+] and Buffering in Arrhythmogenic Failing Rabbit Heart Circ. Res., October 12, 2007; 101(8): 802 - 810. [Abstract] [Full Text] [PDF]

				D. A. Arvanitis, E. Vafiadaki, G.-C. Fan, B. A. Mitton, K. N. Gregory, F. Del Monte, A. Kontrogianni-Konstantopoulos, D. Sanoudou, and E. G. Kranias Histidine-rich Ca-binding protein interacts with sarcoplasmic reticulum Ca-ATPase Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1581 - H1589. [Abstract] [Full Text] [PDF]

				D. Terentyev, S. Viatchenko-Karpinski, S. Vedamoorthyrao, S. Oduru, I. Gyorke, S. C. Williams, and S. Gyorke Protein protein interactions between triadin and calsequestrin are involved in modulation of sarcoplasmic reticulum calcium release in cardiac myocytes J. Physiol., August 15, 2007; 583(1): 71 - 80. [Abstract] [Full Text] [PDF]

				H. E. D. J. ter Keurs and P. A. Boyden Calcium and Arrhythmogenesis Physiol Rev, April 1, 2007; 87(2): 457 - 506. [Abstract] [Full Text] [PDF]

				E. Picht, J. DeSantiago, L. A. Blatter, and D. M. Bers Cardiac Alternans Do Not Rely on Diastolic Sarcoplasmic Reticulum Calcium Content Fluctuations Circ. Res., September 29, 2006; 99(7): 740 - 748. [Abstract] [Full Text] [PDF]

				X. Wu and D. M. Bers Sarcoplasmic Reticulum and Nuclear Envelope Are One Highly Interconnected Ca2+ Store Throughout Cardiac Myocyte Circ. Res., August 4, 2006; 99(3): 283 - 291. [Abstract] [Full Text] [PDF]

				G. Iribe, P. Kohl, and D. Noble Modulatory effect of calmodulin-dependent kinase II (CaMKII) on sarcoplasmic reticulum Ca2+ handling and interval-force relations: a modelling study Phil Trans R Soc A, May 15, 2006; 364(1842): 1107 - 1133. [Abstract] [Full Text] [PDF]

				D. Terentyev, A. Nori, M. Santoro, S. Viatchenko-Karpinski, Z. Kubalova, I. Gyorke, R. Terentyeva, S. Vedamoorthyrao, N. A. Blom, G. Valle, et al. Abnormal Interactions of Calsequestrin With the Ryanodine Receptor Calcium Release Channel Complex Linked to Exercise-Induced Sudden Cardiac Death Circ. Res., May 12, 2006; 98(9): 1151 - 1158. [Abstract] [Full Text] [PDF]

				B. S. Launikonis, J. Zhou, L. Royer, T. R. Shannon, G. Brum, and E. Rios Depletion "skraps" and dynamic buffering inside the cellular calcium store PNAS, February 21, 2006; 103(8): 2982 - 2987. [Abstract] [Full Text] [PDF]

				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]

				L.-S. Song, Y. Pi, S.-J. Kim, A. Yatani, S. Guatimosim, R. K. Kudej, Q. Zhang, H. Cheng, L. Hittinger, B. Ghaleh, et al. Paradoxical Cellular Ca2+ Signaling in Severe but Compensated Canine Left Ventricular Hypertrophy Circ. Res., September 2, 2005; 97(5): 457 - 464. [Abstract] [Full Text] [PDF]

				B. S. Launikonis, J. Zhou, L. Royer, T. R. Shannon, G. Brum, and E. Rios Confocal imaging of [Ca2+] in cellular organelles by SEER, shifted excitation and emission ratioing of fluorescence J. Physiol., September 1, 2005; 567(2): 523 - 543. [Abstract] [Full Text] [PDF]

				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]

				X.-R. Yang, M.-J. Lin, K.-P. Yip, L. H. Jeyakumar, S. Fleischer, G. P. H. Leung, and J. S. K. Sham Multiple ryanodine receptor subtypes and heterogeneous ryanodine receptor-gated Ca2+ stores in pulmonary arterial smooth muscle cells Am J Physiol Lung Cell Mol Physiol, August 1, 2005; 289(2): L338 - L348. [Abstract] [Full Text] [PDF]

				K. Ouyang, C. Wu, and H. Cheng Ca2+-induced Ca2+ Release in Sensory Neurons: LOW GAIN AMPLIFICATION CONFERS INTRINSIC STABILITY J. Biol. Chem., April 22, 2005; 280(16): 15898 - 15902. [Abstract] [Full Text] [PDF]

				D. X. P. Brochet, D. Yang, A. D. Maio, W. J. Lederer, C. Franzini-Armstrong, and H. Cheng Ca2+ blinks: Rapid nanoscopic store calcium signaling PNAS, February 22, 2005; 102(8): 3099 - 3104. [Abstract] [Full Text] [PDF]

				Z. Yang and D. S. Steele Characteristics of Prolonged Ca2+ Release Events Associated With the Nuclei in Adult Cardiac Myocytes Circ. Res., January 7, 2005; 96(1): 82 - 90. [Abstract] [Full Text] [PDF]

				Z. Kubalova, I. Gyorke, R. Terentyeva, S. Viatchenko-Karpinski, D. Terentyev, S. C Williams, and S. Gyorke Modulation of cytosolic and intra-sarcoplasmic reticulum calcium waves by calsequestrin in rat cardiac myocytes J. Physiol., December 1, 2004; 561(2): 515 - 524. [Abstract] [Full Text] [PDF]

				T. J. Hund and Y. Rudy Rate Dependence and Regulation of Action Potential and Calcium Transient in a Canine Cardiac Ventricular Cell Model Circulation, November 16, 2004; 110(20): 3168 - 3174. [Abstract] [Full Text] [PDF]

				A. Gwanyanya, B. Amuzescu, S. I. Zakharov, R. Macianskiene, K. R. Sipido, V. M. Bolotina, J. Vereecke, and K. Mubagwa Magnesium-inhibited, TRPM6/7-like channel in cardiac myocytes: permeation of divalent cations and pH-mediated regulation J. Physiol., September 15, 2004; 559(3): 761 - 776. [Abstract] [Full Text] [PDF]

				R. A. Bassani, J. Altamirano, J. L. Puglisi, and D. M. Bers Action potential duration determines sarcoplasmic reticulum Ca2+ reloading in mammalian ventricular myocytes J. Physiol., September 1, 2004; 559(2): 593 - 609. [Abstract] [Full Text] [PDF]

				D. B. Zorov, E. Kobrinsky, M. Juhaszova, and S. J. Sollott Examining Intracellular Organelle Function Using Fluorescent Probes: From Animalcules to Quantum Dots Circ. Res., August 6, 2004; 95(3): 239 - 252. [Abstract] [Full Text] [PDF]

				S.-Q. Wang, C. Wei, G. Zhao, D. X.P. Brochet, J. Shen, L.-S. Song, W. Wang, D. Yang, and H. Cheng Imaging Microdomain Ca2+ in Muscle Cells Circ. Res., April 30, 2004; 94(8): 1011 - 1022. [Abstract] [Full Text] [PDF]

				K. S. Ginsburg and D. M. Bers Modulation of excitation-contraction coupling by isoproterenol in cardiomyocytes with controlled SR Ca2+ load and Ca2+ current trigger J. Physiol., April 15, 2004; 556(2): 463 - 480. [Abstract] [Full Text] [PDF]

				K. R. Sipido Understanding Cardiac Alternans: The Answer Lies in the Ca2+ Store Circ. Res., March 19, 2004; 94(5): 570 - 572. [Full Text] [PDF]

				S. Q. Wang, M. D. Stern, E. Rios, and H. Cheng The quantal nature of Ca2+ sparks and in situ operation of the ryanodine receptor array in cardiac cells PNAS, March 16, 2004; 101(11): 3979 - 3984. [Abstract] [Full Text] [PDF]

				T. R. Shannon, S. M. Pogwizd, and D. M. Bers Elevated Sarcoplasmic Reticulum Ca2+ Leak in Intact Ventricular Myocytes From Rabbits in Heart Failure Circ. Res., October 3, 2003; 93(7): 592 - 594. [Abstract] [Full Text] [PDF]

				L. Venetucci, A.W. Trafford, and D.A. Eisner Illuminating Sarcoplasmic Reticulum Calcium Circ. Res., July 11, 2003; 93(1): 4 - 5. [Full Text] [PDF]