© 2000 American Heart Association, Inc.
Review |
Integrative Analysis of Calcium Cycling in Cardiac Muscle
From the Unit of Cardiac Physiology, University of Manchester, UK.
Correspondence to D.A. Eisner, Unit of Cardiac Physiology, University of Manchester, 1.524 Stopford Bldg, Oxford Rd, Manchester M13 9PT, UK. E-mail Eisner{at}man.ac.uk
Abstract—The control of intracellular calcium is central to regulation of contractile force in cardiac muscle. This review illustrates how analysis of the control of calcium requires an integrated approach in which several systems are considered. Thus, the calcium content of the sarcoplasmic reticulum (SR) is a major determinant of the amount of Ca2+ released from the SR and the amplitude of the Ca2+ transient. The amplitude of the transient, in turn, controls Ca2+ fluxes across the sarcolemma and thence SR content. This control of SR content influences the response to maneuvers that modify, for example, the properties of the SR Ca2+ release channel or ryanodine receptor. Specifically, modulation of the open probability of the ryanodine receptor produces only transient effects on the Ca2+ transient as a result of changes of SR content. These interactions between various Ca2+ fluxes are modified by the Ca2+ buffering properties of the cell. Finally, we predict that, under some conditions, the above interactions can result in instability (such as alternans) rather than ordered control of contractility.
Key Words: excitation-contraction coupling • sarcoplasmic reticulum • ryanodine receptor
This article has been cited by other articles:
 |
|
 |
|
  T. Tao, S. C. O'Neill, M. E. Diaz, Y. T. Li, D. A. Eisner, and H. Zhang Alternans of cardiac calcium cycling in a cluster of ryanodine receptors: a simulation study Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H598 - H609. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Mangoni and J. Nargeot Genesis and Regulation of the Heart Automaticity Physiol Rev, July 1, 2008; 88(3): 919 - 982. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ozdemir, V. Bito, P. Holemans, L. Vinet, J.-J. Mercadier, A. Varro, and K. R. Sipido Pharmacological Inhibition of Na/Ca Exchange Results in Increased Cellular Ca2+ Load Attributable to the Predominance of Forward Mode Block Circ. Res., June 6, 2008; 102(11): 1398 - 1405. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. J. Wang and E. A. Sobie Mathematical model of the neonatal mouse ventricular action potential Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2565 - H2575. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Murphy and C. Steenbergen Ion Transport and Energetics During Cell Death and Protection Physiology, April 1, 2008; 23(2): 115 - 123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Murphy and C. Steenbergen Mechanisms Underlying Acute Protection From Cardiac Ischemia-Reperfusion Injury Physiol Rev, April 1, 2008; 88(2): 581 - 609. [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]
|
|
|
|
|
|
T. Seidler, G. Hasenfuss, and L. S. Maier Targeting Altered Calcium Physiology in the Heart: Translational Approaches to Excitation, Contraction, and Transcription Physiology, October 1, 2007; 22(5): 328 - 334. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Seddon, A. M. Shah, and B. Casadei Cardiomyocytes as effectors of nitric oxide signalling Cardiovasc Res, July 15, 2007; 75(2): 315 - 326. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Livshitz and Y. Rudy Regulation of Ca2+ and electrical alternans in cardiac myocytes: role of CAMKII and repolarizing currents Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2854 - H2866. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-C. Chou, S. Zhou, H. Hayashi, M. Nihei, Y.-B. Liu, M.-S. Wen, S.-J. Yeh, M. C. Fishbein, J. N. Weiss, S.-F. Lin, et al. Remodelling of action potential and intracellular calcium cycling dynamics during subacute myocardial infarction promotes ventricular arrhythmias in Langendorff-perfused rabbit hearts J. Physiol., May 1, 2007; 580(3): 895 - 906. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. M. Kravtsov, K. W. L. Kam, J. Liu, S. Wu, and T. M. Wong Altered Ca2+ handling by ryanodine receptor and Na+-Ca2+ exchange in the heart from ovariectomized rats: role of protein kinase A Am J Physiol Cell Physiol, May 1, 2007; 292(5): C1625 - C1635. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kawai, T. Kawai, J. T. Sambol, D.-Z. Xu, Z. Yuan, F. J. Caputo, C. D. Badami, E. A. Deitch, and A. Yatani Cellular mechanisms of burn-related changes in contractility and its prevention by mesenteric lymph ligation Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2475 - H2484. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Noble From the Hodgkin-Huxley axon to the virtual heart J. Physiol., April 1, 2007; 580(1): 15 - 22. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Mattiazzi, L. Vittone, and C. Mundina-Weilenmann Ca2+/calmodulin-dependent protein kinase: A key component in the contractile recovery from acidosis Cardiovasc Res, March 1, 2007; 73(4): 648 - 656. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Sato, Y. Shiferaw, Z. Qu, A. Garfinkel, J. N. Weiss, and A. Karma Inferring the Cellular Origin of Voltage and Calcium Alternans from the Spatial Scales of Phase Reversal during Discordant Alternans Biophys. J., February 15, 2007; 92(4): L33 - L35. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Pott, X. Ren, D. X. Tran, M.-J. Yang, S. Henderson, M. C. Jordan, K. P. Roos, A. Garfinkel, K. D. Philipson, and J. I. Goldhaber Mechanism of shortened action potential duration in Na+-Ca2+ exchanger knockout mice Am J Physiol Cell Physiol, February 1, 2007; 292(2): C968 - C973. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Bers Altered Cardiac Myocyte Ca Regulation In Heart Failure. Physiology, December 1, 2006; 21(6): 380 - 387. [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]
|
|
|
|
|
|
G. L. Aistrup, J. E. Kelly, S. Kapur, M. Kowalczyk, I. Sysman-Wolpin, A. H. Kadish, and J. A. Wasserstrom Pacing-induced Heterogeneities in Intracellular Ca2+ Signaling, Cardiac Alternans, and Ventricular Arrhythmias in Intact Rat Heart Circ. Res., September 29, 2006; 99(7): E65 - E73. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Sato, Y. Shiferaw, A. Garfinkel, J. N. Weiss, Z. Qu, and A. Karma Spatially Discordant Alternans in Cardiac Tissue: Role of Calcium Cycling Circ. Res., September 1, 2006; 99(5): 520 - 527. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Nakayama, B. J. Wilkin, I. Bodi, and J. D. Molkentin Calcineurin-dependent cardiomyopathy is activated by TRPC in the adult mouse heart FASEB J, August 1, 2006; 20(10): 1660 - 1670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Orchard T-tubule trouble J. Physiol., July 15, 2006; 574(2): 330 - 330. [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Shiferaw and A. Karma Turing instability mediated by voltage and calcium diffusion in paced cardiac cells PNAS, April 11, 2006; 103(15): 5670 - 5675. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Sun, E. Picht, K. S. Ginsburg, D. M. Bers, C. Steenbergen, and E. Murphy Hypercontractile Female Hearts Exhibit Increased S-Nitrosylation of the L-Type Ca2+ Channel {alpha}1 Subunit and Reduced Ischemia/Reperfusion Injury Circ. Res., February 17, 2006; 98(3): 403 - 411. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-Z. Yang, J. Kockskamper, F. R. Heinzel, M. Hauber, S. Walther, J. Spiess, and B. Pieske Urocortin II enhances contractility in rabbit ventricular myocytes via CRF2 receptor-mediated stimulation of protein kinase A Cardiovasc Res, February 1, 2006; 69(2): 402 - 411. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. N. Jordan and D. J. Christini Action Potential Morphology Influences Intracellular Calcium Handling Stability and the Occurrence of Alternans Biophys. J., January 15, 2006; 90(2): 672 - 680. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Brette, L. Salle, and C. H. Orchard Quantification of Calcium Entry at the T-Tubules and Surface Membrane in Rat Ventricular Myocytes Biophys. J., January 1, 2006; 90(1): 381 - 389. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Qu Critical mass hypothesis revisited: role of dynamical wave stability in spontaneous termination of cardiac fibrillation Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H255 - H263. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. N. Weiss, Z. Qu, P.-S. Chen, S.-F. Lin, H. S. Karagueuzian, H. Hayashi, A. Garfinkel, and A. Karma The Dynamics of Cardiac Fibrillation Circulation, August 23, 2005; 112(8): 1232 - 1240. [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]
|
|
|
|
 |
|
 D. A. Eisner, M. E. Diaz, Y. Li, S. C. O'Neill, and A. W. Trafford Stability and instability of regulation of intracellular calcium Exp Physiol, January 1, 2005; 90(1): 3 - 12. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Lakireddy, P. Baweja, A. Syed, G. Bub, M. Boutjdir, and N. El-Sherif Contrasting effects of ischemia on the kinetics of membrane voltage and intracellular calcium transient underlie electrical alternans Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H400 - H407. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Seth, C. Sumbilla, S. P. Mullen, D. Lewis, M. G. Klein, A. Hussain, J. Soboloff, D. L. Gill, and G. Inesi Sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) gene silencing and remodeling of the Ca2+ signaling mechanism in cardiac myocytes PNAS, November 23, 2004; 101(47): 16683 - 16688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Lowri Thomas, C. H. George, and F. Anthony Lai Functional heterogeneity of ryanodine receptor mutations associated with sudden cardiac death Cardiovasc Res, October 1, 2004; 64(1): 52 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Eisner and K. R. Sipido Sodium Calcium Exchange in the Heart: Necessity or Luxury? Circ. Res., September 17, 2004; 95(6): 549 - 551. [Full Text] [PDF]
|
|
|
|
|
|
S. A. Grandy, E. M. Denovan-Wright, G. R. Ferrier, and S. E. Howlett Overexpression of human {beta}2-adrenergic receptors increases gain of excitation-contraction coupling in mouse ventricular myocytes Am J Physiol Heart Circ Physiol, September 1, 2004; 287(3): H1029 - H1038. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. E. Bondarenko, G. P. Szigeti, G. C. L. Bett, S.-J. Kim, and R. L. Rasmusson Computer model of action potential of mouse ventricular myocytes Am J Physiol Heart Circ Physiol, September 1, 2004; 287(3): H1378 - H1403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Noble Modeling the Heart Physiology, August 1, 2004; 19(4): 191 - 197. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Brette, L. Salle, and C. H. Orchard Differential Modulation of L-type Ca2+ Current by SR Ca2+ Release at the T-Tubules and Surface Membrane of Rat Ventricular Myocytes Circ. Res., July 9, 2004; 95(1): e1 - e7. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wang and J. I. Goldhaber Return of calcium: Manipulating intracellular calcium to prevent cardiac pathologies PNAS, April 20, 2004; 101(16): 5697 - 5698. [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]
|
|
|
|
|
|
M. E. Diaz, S. C. O'Neill, and D. A. Eisner Sarcoplasmic Reticulum Calcium Content Fluctuation Is the Key to Cardiac Alternans Circ. Res., March 19, 2004; 94(5): 650 - 656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Tavi, S. Pikkarainen, J. Ronkainen, P. Niemela, M. Ilves, M. Weckstrom, O. Vuolteenaho, J. Bruton, H. Westerblad, and H. Ruskoaho Pacing-induced calcineurin activation controls cardiac Ca2+ signalling and gene expression J. Physiol., January 15, 2004; 554(2): 309 - 320. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. D. Nearing and R. L. Verrier Tracking cardiac electrical instability by computing interlead heterogeneity of T-wave morphology J Appl Physiol, December 1, 2003; 95(6): 2265 - 2272. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Shiferaw, M. A. Watanabe, A. Garfinkel, J. N. Weiss, and A. Karma Model of Intracellular Calcium Cycling in Ventricular Myocytes Biophys. J., December 1, 2003; 85(6): 3666 - 3686. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Chen, J. Petranka, K. Yamamura, R. E. London, C. Steenbergen, and E. Murphy Gender differences in sarcoplasmic reticulum calcium loading after isoproterenol Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2657 - H2662. [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]
|
|
|
|
|
|
T. Seidler, S. L.W. Miller, C. M. Loughrey, A. Kania, A. Burow, S. Kettlewell, N. Teucher, S. Wagner, H. Kogler, M. B. Meyers, et al. Effects of Adenovirus-Mediated Sorcin Overexpression on Excitation-Contraction Coupling in Isolated Rabbit Cardiomyocytes Circ. Res., July 25, 2003; 93(2): 132 - 139. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Verrier, A. V. Tolat, and M. E. Josephson T-Wave alternans for arrhythmia risk stratification in patients with idiopathic dilated cardiomyopathy J. Am. Coll. Cardiol., June 18, 2003; 41(12): 2225 - 2227. [Full Text] [PDF]
|
|
|
|
|
|
S. J. Liu, R. H. Kennedy, M. H. Creer, and J. McHowat Alterations in Ca2+ cycling by lysoplasmenylcholine in adult rabbit ventricular myocytes Am J Physiol Cell Physiol, April 1, 2003; 284(4): C826 - C838. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Weisser-Thomas, V. Piacentino III, J. P Gaughan, K. Margulies, and S. R Houser Calcium entry via Na/Ca exchange during the action potential directly contributes to contraction of failing human ventricular myocytes Cardiovasc Res, March 15, 2003; 57(4): 974 - 985. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D.A. Eisner and A.W. Trafford Heart Failure and the Ryanodine Receptor: Does Occam's Razor Rule? Circ. Res., November 29, 2002; 91(11): 979 - 981. [Full Text] [PDF]
|
|
|
|
|
|
M. Nishio, S. W. Ruch, and J. A. Wasserstrom Positive inotropic effects of ouabain in isolated cat ventricular myocytes in sodium-free conditions Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H2045 - H2053. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. D. Nearing and R. L. Verrier Progressive Increases in Complexity of T-Wave Oscillations Herald Ischemia-Induced Ventricular Fibrillation Circ. Res., October 18, 2002; 91(8): 727 - 732. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.E. Diaz, D.A. Eisner, and S.C. O'Neill Depressed Ryanodine Receptor Activity Increases Variability and Duration of the Systolic Ca2+ Transient in Rat Ventricular Myocytes Circ. Res., October 4, 2002; 91(7): 585 - 593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Yang, C. Pascarel, D.S. Steele, K. Komukai, F. Brette, and C.H. Orchard Na+-Ca2+ Exchange Activity Is Localized in the T-Tubules of Rat Ventricular Myocytes Circ. Res., August 23, 2002; 91(4): 315 - 322. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Young, P. H. Guthrie, P. Razeghi, B. Leighton, S. Abbasi, S. Patil |