Circulation Research. 2003;93:487-490
doi: 10.1161/01.RES.0000091871.54907.6B
doi: 10.1161/01.RES.0000091871.54907.6B
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2003 American Heart Association, Inc.
Editorial |
Sarcoplasmic Reticulum Ca2+ and Heart Failure
Roles of Diastolic Leak and Ca2+ Transport
From the Department of Physiology (D.M.B.), Loyola University Chicago, Maywood Ill; Department of Medicine (D.A.E.), University of Manchester, Manchester, UK; and Department of Physiology (H.H.V.), University of Wisconsin, Madison Wis.
Correspondence to Donald M. Bers, Department of Physiology, Loyola University Chicago, 2160 S First Ave, Maywood, IL 60153. E-mail dbers@lumc.edu; and Héctor H. Valdivia, Department of Physiology, University of Wisconsin Medical School, 1300 University Ave, Madison, WI 53706. E-mail valdivia@physiology.wisc.edu
Key Words: heart failure • ryanodine receptors • calcium sparks
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Heart failure (HF) is a leading cause of death and enormous effort has focused at understanding the molecular and cellular mechanisms of the decreased cardiac contractility. While changes of other components contribute, it is generally agreed that much of the contractile deficit is due to reduced myocyte Ca2+ transients.1,2 Alterations in Ca2+ current (ICa) and action potential characteristics are also seen in HF, but a central factor limiting Ca2+ transient amplitude is a decrease of sarcoplasmic reticulum (SR) Ca2+ content.3–6 HF is extremely complex, but it is easy to appreciate how reduced SR Ca2+ content would reduce SR Ca2+ release, myofilament activation, and contractility. Despite agreement that SR Ca2+ content is reduced in HF, controversy exists about why SR content is low.
How Is SR Ca2+ Content Decreased in Heart Failure?
SR Ca2+ content reflects the balance between Ca2+ uptake (via SERCA) and Ca2+ efflux via ryanodine receptor (RyR). Thus, reduced SR content in HF must be due to reduced Ca2+ pumping by SERCA or increased SR Ca2+ leak via RyRs. Both are supported by experimental data (below). Transsarcolemmal Ca2+ fluxes also affect SR Ca2+ load. That is, reduced Ca2+ influx (eg, via ICa) or enhanced Ca2+ extrusion via Na+-Ca2+ exchange (NCX) can unload the SR. Results are not unanimous, but most groups find little alteration in peak ICa density in HF, while many find evidence of enhanced NCX expression and function.1,2 Increased NCX function can compete with SERCA during [Ca2+]i decline, extruding more Ca2+ from the cell and depleting the SR. In the
Related Article:
Circ. Res. 2005 96: 847-855.
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]
|
|
|
|
 |
|
 P. A. Boyden The failing ventricle: what initiates the complex ventricular arrhythmias? Am J Physiol Heart Circ Physiol, October 1, 2009; 297(4): H1198 - H1199. [Full Text] [PDF]
|
|
|
|
|
|
P. J. Schaeffer, J. DeSantiago, J. Yang, T. P. Flagg, A. Kovacs, C. J. Weinheimer, M. Courtois, T. C. Leone, C. G. Nichols, D. M. Bers, et al. Impaired contractile function and calcium handling in hearts of cardiac-specific calcineurin b1-deficient mice Am J Physiol Heart Circ Physiol, October 1, 2009; 297(4): H1263 - H1273. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Guinto, T. E. Haim, C. C. Dowell-Martino, N. Sibinga, and J. C. Tardiff Temporal and mutation-specific alterations in Ca2+ homeostasis differentially determine the progression of cTnT-related cardiomyopathies in murine models Am J Physiol Heart Circ Physiol, August 1, 2009; 297(2): H614 - H626. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. R. Shannon and W. Y.W. Lew Diastolic release of calcium from the sarcoplasmic reticulum: a potential target for treating triggered arrhythmias and heart failure. J. Am. Coll. Cardiol., May 26, 2009; 53(21): 2006 - 2008. [Full Text] [PDF]
|
|
|
|
|
|
Q. Yuan, P. Han, M. Dong, X. Ren, X. Zhou, S. Chen, W. K. Jones, G. Chu, H.-S. Wang, and E. G. Kranias Partial downregulation of junctin enhances cardiac calcium cycling without eliciting ventricular arrhythmias in mice Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1484 - H1490. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Gomez, A. Rueda, Y. Sainte-Marie, L. Pereira, S. Zissimopoulos, X. Zhu, R. Schaub, E. Perrier, R. Perrier, C. Latouche, et al. Mineralocorticoid Modulation of Cardiac Ryanodine Receptor Activity Is Associated With Downregulation of FK506-Binding Proteins Circulation, April 28, 2009; 119(16): 2179 - 2187. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Hilal-Dandan, H. He, J. L. Martin, L. L. Brunton, and W. H. Dillmann Endothelin downregulates SERCA2 gene and protein expression in adult rat ventricular myocytes: regulation by pertussis toxin-sensitive Gi protein and cAMP Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H728 - H734. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Terentyev, A. E. Belevych, R. Terentyeva, M. M. Martin, G. E. Malana, D. E. Kuhn, M. Abdellatif, D. S. Feldman, T. S. Elton, and S. Gyorke miR-1 Overexpression Enhances Ca2+ Release and Promotes Cardiac Arrhythmogenesis by Targeting PP2A Regulatory Subunit B56{alpha} and Causing CaMKII-Dependent Hyperphosphorylation of RyR2 Circ. Res., February 27, 2009; 104(4): 514 - 521. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Antoons and K. R. Sipido Targeting calcium handling in arrhythmias Europace, December 1, 2008; 10(12): 1364 - 1369. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Pavlopoulos, J. Grapsa, E. Stefanadi, E. Philippou, D. Dawson, and P. Nihoyannopoulos Is it only diastolic dysfunction? Segmental relaxation patterns and longitudinal systolic deformation in systemic hypertension Eur J Echocardiogr, November 1, 2008; 9(6): 741 - 747. [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]
|
|
|
|
|
|
J. Davis, M. V. Westfall, D. Townsend, M. Blankinship, T. J. Herron, G. Guerrero-Serna, W. Wang, E. Devaney, and J. M. Metzger Designing Heart Performance by Gene Transfer Physiol Rev, October 1, 2008; 88(4): 1567 - 1651. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Shenouda, K. C. Lord, E. McIlwain, P. A. Lucchesi, and K. J. Varner Ecstasy produces left ventricular dysfunction and oxidative stress in rats Cardiovasc Res, September 1, 2008; 79(4): 662 - 670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zhu, A. A. Gach, G. Liu, X. Xu, C. C. Lim, J. X. Zhang, L. Mao, K. Chuprun, W. J. Koch, R. Liao, et al. Enhanced calcium cycling and contractile function in transgenic hearts expressing constitutively active G{alpha}o* protein Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1335 - H1347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Orchard and F. Brette t-tubules and sarcoplasmic reticulum function in cardiac ventricular myocytes Cardiovasc Res, January 15, 2008; 77(2): 237 - 244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. H. George Sarcoplasmic reticulum Ca2+ leak in heart failure: mere observation or functional relevance? Cardiovasc Res, January 15, 2008; 77(2): 302 - 314. [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. Medeiros, N. P. L. Rolim, R. S. F. Oliveira, K. T. Rosa, K. C. Mattos, D. E. Casarini, M. C. Irigoyen, E. M. Krieger, J. E. Krieger, C. E. Negrao, et al. Exercise training delays cardiac dysfunction and prevents calcium handling abnormalities in sympathetic hyperactivity-induced heart failure mice J Appl Physiol, January 1, 2008; 104(1): 103 - 109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Xiao, X. Tian, W. Xie, P. P. Jones, S. Cai, X. Wang, D. Jiang, H. Kong, L. Zhang, K. Chen, et al. Functional Consequence of Protein Kinase A-dependent Phosphorylation of the Cardiac Ryanodine Receptor: SENSITIZATION OF STORE OVERLOAD-INDUCED Ca2+ RELEASE J. Biol. Chem., October 12, 2007; 282(41): 30256 - 30264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. A. Benkusky, C. S. Weber, J. A. Scherman, E. F. Farrell, T. A. Hacker, M. C. John, P. A. Powers, and H. H. Valdivia Intact {beta}-Adrenergic Response and Unmodified Progression Toward Heart Failure in Mice With Genetic Ablation of a Major Protein Kinase A Phosphorylation Site in the Cardiac Ryanodine Receptor Circ. Res., October 12, 2007; 101(8): 819 - 829. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Chen-Izu, C. W. Ward, W. Stark Jr., T. Banyasz, M. P. Sumandea, C. W. Balke, L. T. Izu, and X. H. T. Wehrens Phosphorylation of RyR2 and shortening of RyR2 cluster spacing in spontaneously hypertensive rat with heart failure Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2409 - H2417. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. R. Lamberts, E. Caldenhoven, M. Lansink, G. Witte, R. J. Vaessen, J. A. St Cyr, and G. J. M. Stienen Preservation of diastolic function in monocrotaline-induced right ventricular hypertrophy in rats Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1869 - H1876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-G. Kerfant, D. Zhao, I. Lorenzen-Schmidt, L. S. Wilson, S. Cai, S. R. W. Chen, D. H. Maurice, and P. H. Backx PI3K{gamma} Is Required for PDE4, not PDE3, Activity in Subcellular Microdomains Containing the Sarcoplasmic Reticular Calcium ATPase in Cardiomyocytes Circ. Res., August 17, 2007; 101(4): 400 - 408. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. R. Lamberts, N. Hamdani, T. W. Soekhoe, N. M. Boontje, R. Zaremba, L. A. Walker, P. P. de Tombe, J. van der Velden, and G. J. M. Stienen Frequency-dependent myofilament Ca2+ desensitization in failing rat myocardium J. Physiol., July 15, 2007; 582(2): 695 - 709. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Gergs, T. Berndt, J. Buskase, L. R. Jones, U. Kirchhefer, F. U. Muller, K.-D. Schluter, W. Schmitz, and J. Neumann On the role of junctin in cardiac Ca2+ handling, contractility, and heart failure Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H728 - H734. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Prasad, H. Ma, C. Sumbilla, D. I. Lee, M. G. Klein, and G. Inesi Phenylephrine hypertrophy, Ca2+-ATPase (SERCA2), and Ca2+ signaling in neonatal rat cardiac myocytes Am J Physiol Cell Physiol, June 1, 2007; 292(6): C2269 - C2275. [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]
|
|
|
|
|
|
S. Hayoz, J.-L. Beny, and R. Bychkov Intracellular cAMP: the "switch" that triggers on "spontaneous transient outward currents" generation in freshly isolated myocytes from thoracic aorta Am J Physiol Cell Physiol, April 1, 2007; 292(4): C1502 - C1509. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. S. Maier and D. M. Bers Role of Ca2+/calmodulin-dependent protein kinase (CaMK) in excitation-contraction coupling in the heart Cardiovasc Res, March 1, 2007; 73(4): 631 - 640. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. Sipido CaM or cAMP: Linking {beta}-Adrenergic Stimulation to 'Leaky' RyRs Circ. Res., February 16, 2007; 100(3): 296 - 298. [Full Text] [PDF]
|
|
|
|
|
|
J. Curran, M. J. Hinton, E. Rios, D. M. Bers, and T. R. Shannon {beta}-Adrenergic Enhancement of Sarcoplasmic Reticulum Calcium Leak in Cardiac Myocytes Is Mediated by Calcium/Calmodulin-Dependent Protein Kinase Circ. Res., February 16, 2007; 100(3): 391 - 398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Milting, N. Lukas, B. Klauke, R. Korfer, A. Perrot, K.-J. Osterziel, J. Vogt, S. Peters, R. Thieleczek, and M. Varsanyi Composite polymorphisms in the ryanodine receptor 2 gene associated with arrhythmogenic right ventricular cardiomyopathy Cardiovasc Res, August 1, 2006; 71(3): 496 - 505. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Orchard T-tubule trouble J. Physiol., July 15, 2006; 574(2): 330 - 330. [Full Text] [PDF]
|
|
|
|
 |
|
 L.-S. Song, E. A. Sobie, S. McCulle, W. J. Lederer, C. W. Balke, and H. Cheng Orphaned ryanodine receptors in the failing heart. PNAS, March 14, 2006; 103(11): 4305 - 4310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Litwin "Ryanogate": Who Leaked the Calcium? Circ. Res., February 3, 2006; 98(2): 165 - 168. [Full Text] [PDF]
|
|
|
|
|
|
Y. Ji, W. Zhao, B. Li, J. Desantiago, E. Picht, M. A. Kaetzel, J. E. J. Schultz, E. G. Kranias, D. M. Bers, and J. R. Dedman Targeted inhibition of sarcoplasmic reticulum CaMKII activity results in alterations of Ca2+ homeostasis and cardiac contractility Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H599 - H606. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Anderson The Fire From Within: The Biggest Ca2+ Channel Erupts and Dribbles Circ. Res., December 9, 2005; 97(12): 1213 - 1215. [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
J. Fauconnier, A. Lacampagne, J.-M. Rauzier, G. Vassort, and S. Richard Ca2+-dependent reduction of IK1 in rat ventricular cells: A novel paradigm for arrhythmia in heart failure? Cardiovasc Res, November 1, 2005; 68(2): 204 - 212. [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]
|
|
|
|
|
|
S. Viatchenko-Karpinski, D. Terentyev, L. A. Jenkins, L. O. Lutherer, and S. Gyorke Synergistic interactions between Ca2+ entries through L-type Ca2+ channels and Na+-Ca2+ exchanger in normal and failing rat heart J. Physiol., September 1, 2005; 567(2): 493 - 504. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. H. T. Wehrens, S. E. Lehnart, S. Reiken, R. van der Nagel, R. Morales, J. Sun, Z. Cheng, S.-X. Deng, L. J. de Windt, D. W. Landry, et al. Enhancing calstabin binding to ryanodine receptors improves cardiac and skeletal muscle function in heart failure PNAS, July 5, 2005; 102(27): 9607 - 9612. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Ahlers, J. Song, J. Wang, X.-Q. Zhang, L. L. Carl, G. M. Tadros, L. I. Rothblum, and J. Y. Cheung Effects of sarcoplasmic reticulum Ca2+-ATPase overexpression in postinfarction rat myocytes J Appl Physiol, June 1, 2005; 98(6): 2169 - 2176. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-G. Kerfant, D. Gidrewicz, H. Sun, G. Y. Oudit, J. M. Penninger, and P. H. Backx Cardiac Sarcoplasmic Reticulum Calcium Release and Load Are Enhanced by Subcellular cAMP Elevations in PI3K{gamma}-Deficient Mice Circ. Res., May 27, 2005; 96(10): 1079 - 1086. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Xiao, M. T. Jiang, M. Zhao, D. Yang, C. Sutherland, F. A. Lai, M. P. Walsh, D. C. Warltier, H. Cheng, and S. R. W. Chen Characterization of a Novel PKA Phosphorylation Site, Serine-2030, Reveals No PKA Hyperphosphorylation of the Cardiac Ryanodine Receptor in Canine Heart Failure Circ. Res., April 29, 2005; 96(8): 847 - 855. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Lokuta, N. A. Maertz, S. V. Meethal, K. T. Potter, T. J. Kamp, H. H. Valdivia, and R. A. Haworth Increased Nitration of Sarcoplasmic Reticulum Ca2+-ATPase in Human Heart Failure Circulation, March 1, 2005; 111(8): 988 - 995. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J Janse Electrophysiological changes in heart failure and their relationship to arrhythmogenesis Cardiovasc Res, February 1, 2004; 61(2): 208 - 217. [Abstract] [Full Text] [PDF]
|
|