(Circulation. 2000;102:2137.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Enhanced Ca2+ Release and Na/Ca Exchange Activity in Hypertrophied Canine Ventricular Myocytes
Potential Link Between Contractile Adaptation and Arrhythmogenesis
From the Laboratory of Experimental Cardiology (K.R.S., F.v.d.W.) and Department of Physiology (F.V.), University of Leuven, Belgium, and the Department of Cardiology, Academic Hospital Maastricht (P.G.A.V., S.H.M.d.G., H.J.J.W., M.A.V.), Netherlands.
Correspondence to Karin R. Sipido, MD, PhD, Laboratory of Experimental Cardiology, KUL, Campus Gasthuisberg O/N, Herestraat 49, B-3000 Leuven, Belgium. E-mail karin.sipido{at}med.kuleuven.ac.be
Background—Ventricular arrhythmias are a major cause of sudden death in patients with heart failure and hypertrophy. The dog with chronic complete atrioventricular block (CAVB) has biventricular hypertrophy and ventricular arrhythmias and is a useful model to study underlying cellular mechanisms. We investigated whether changes in Ca2+ homeostasis are part of the contractile adaptation to CAVB and might contribute to arrhythmogenesis.
Methods and Results—In enzymatically isolated myocytes, cell shortening, Ca2+ release from the sarcoplasmic reticulum (SR), and SR Ca2+ content were enhanced at low stimulation frequencies. Ca2+ influx through L-type Ca2+ channels was unchanged, but Ca2+ influx via the Na/Ca exchanger was increased and contributed to Ca2+ loading of the SR. Inward Na/Ca exchange currents were also larger. Changes in Ca2+ fluxes were less pronounced in the right versus left ventricle.
Conclusions—Enhanced Na/Ca exchange activity may improve contractile adaptation to CAVB but at the same time facilitate arrhythmias by (1) increasing the propensity to Ca2+ overload, (2) providing more inward current leading to (nonhomogeneous) action potential prolongation, and (3) enhancing (arrhythmogenic) currents during spontaneous Ca2+ release.
Key Words: calcium • myocytes • sarcoplasmic reticulum • hypertrophy
This article has been cited by other articles:
 |
|
 |
|
  X. Qi, Y.-H. Yeh, D. Chartier, L. Xiao, Y. Tsuji, B. J.J.M. Brundel, I. Kodama, and S. Nattel The Calcium/Calmodulin/Kinase System and Arrhythmogenic Afterdepolarizations in Bradycardia-Related Acquired Long-QT Syndrome Circ Arrhythmia Electrophysiol, June 1, 2009; 2(3): 295 - 304. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. F. Decker, J. Heijman, J. R. Silva, T. J. Hund, and Y. Rudy Properties and ionic mechanisms of action potential adaptation, restitution, and accommodation in canine epicardium Am J Physiol Heart Circ Physiol, April 1, 2009; 296(4): H1017 - H1026. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. K. Mork, I. Sjaastad, O. M. Sejersted, and W. E. Louch Slowing of cardiomyocyte Ca2+ release and contraction during heart failure progression in postinfarction mice Am J Physiol Heart Circ Physiol, April 1, 2009; 296(4): H1069 - H1079. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
V. Bito, F. R. Heinzel, L. Biesmans, G. Antoons, and K. R. Sipido Crosstalk between L-type Ca2+ channels and the sarcoplasmic reticulum: alterations during cardiac remodelling Cardiovasc Res, January 15, 2008; 77(2): 315 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Antzelevitch Role of spatial dispersion of repolarization in inherited and acquired sudden cardiac death syndromes Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2024 - H2038. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Antzelevitch Ionic, molecular, and cellular bases of QT-interval prolongation and torsade de pointes Europace, September 1, 2007; 9(suppl_4): iv4 - iv15. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K.G. Winckels, M. B. Thomsen, P. Oosterhoff, A. Oros, J. D.M. Beekman, N. J.M. Attevelt, L. Kretzers, and M. A. Vos High-Septal Pacing Reduces Ventricular Electrical Remodeling and Proarrhythmia in Chronic Atrioventricular Block Dogs J. Am. Coll. Cardiol., August 28, 2007; 50(9): 906 - 913. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Leszek, M. Szperl, A. Klisiewicz, J. Janas, A. Biederman, T. Rywik, W. Piotrowski, M. Kopacz, and J. Korewicki Alteration of myocardial sarcoplasmic reticulum Ca2+-ATPase and Na+-Ca2+ exchanger expression in human left ventricular volume overload Eur J Heart Fail, June 1, 2007; 9(6-7): 579 - 586. [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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 G. Antoons, P. G. A. Volders, T. Stankovicova, V. Bito, M. Stengl, M. A. Vos, and K. R. Sipido Window Ca2+ current and its modulation by Ca2+ release in hypertrophied cardiac myocytes from dogs with chronic atrioventricular block J. Physiol., February 15, 2007; 579(1): 147 - 160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. Thomsen, A. Oros, M. Schoenmakers, J. M. van Opstal, J. N. Maas, J. D.M. Beekman, and M. A. Vos Proarrhythmic electrical remodelling is associated with increased beat-to-beat variability of repolarisation Cardiovasc Res, February 1, 2007; 73(3): 521 - 530. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. R. Carvalho, R. A. Bassani, K. G. Franchini, and J. W. M. Bassani Enhanced calcium mobilization in rat ventricular myocytes during the onset of pressure overload-induced hypertrophy Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1803 - H1813. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Stengl, C. Ramakers, D. W. Donker, A. Nabar, A. V. Rybin, R. L.H.M.G. Spatjens, T. van der Nagel, W. K.W.H. Wodzig, K. R. Sipido, G. Antoons, et al. Temporal patterns of electrical remodeling in canine ventricular hypertrophy: Focus on IKs downregulation and blunted {beta}-adrenergic activation Cardiovasc Res, October 1, 2006; 72(1): 90 - 100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fernandez-Velasco, A. M. Gomez, and S. Richard Unzipping RyR2 in adult cardiomyocytes: Getting closer to mechanisms of inherited ventricular arrhythmias? Cardiovasc Res, June 1, 2006; 70(3): 407 - 409. [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]
|
|
|
|
|
|
M. R. Fowler, J. R. Naz, M. D. Graham, G. Bru-Mercier, S. M. Harrison, and C. H. Orchard Decreased Ca2+ extrusion via Na+/Ca2+ exchange in epicardial left ventricular myocytes during compensated hypertrophy Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2431 - H2438. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Jung, M. P. Quaile, G. D. Mills, D. P. Bednarik, S. R. Houser, and K. B. Margulies Pharmacological Effects of ATI22-107 [2-(2-{2-[2-Chloro-4-(6-oxo-1,4,5,6-tetrahydro-pyridazin-3-yl)-phenoxy]-acetylamino}-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-1,4-dihydro-pyridine-3,5-dicarboxylic Acid Dimethyl Ester)], a Novel Dual Pharmacophore, on Myocyte Calcium Cycling and Contractility J. Pharmacol. Exp. Ther., February 1, 2005; 312(2): 517 - 524. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Antzelevitch Cardiac repolarization. The long and short of it Europace, January 1, 2005; 7(s2): S3 - S9. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Baartscheer, C. A. Schumacher, M. M.G.J. van Borren, C. N.W. Belterman, R. Coronel, T. Opthof, and J. W.T. Fiolet Chronic inhibition of Na+/H+-exchanger attenuates cardiac hypertrophy and prevents cellular remodeling in heart failure Cardiovasc Res, January 1, 2005; 65(1): 83 - 92. [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]
|
|
|
|
 |
|
 I. A. Hobai, C. Maack, and B. O'Rourke Partial Inhibition of Sodium/Calcium Exchange Restores Cellular Calcium Handling in Canine Heart Failure Circ. Res., August 6, 2004; 95(3): 292 - 299. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.E Diaz, H.K Graham, and A.W Trafford Enhanced sarcolemmal Ca2+ efflux reduces sarcoplasmic reticulum Ca2+ content and systolic Ca2+ in cardiac hypertrophy Cardiovasc Res, June 1, 2004; 62(3): 538 - 547. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Canty Jr, G. Suzuki, M. D. Banas, F. Verheyen, M. Borgers, and J. A. Fallavollita Hibernating Myocardium: Chronically Adapted to Ischemia but Vulnerable to Sudden Death Circ. Res., April 30, 2004; 94(8): 1142 - 1149. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Wasson, H. K. Reddy, and M. L. Dohrmann Current Perspectives of Electrical Remodeling and Its Therapeutic Implications Journal of Cardiovascular Pharmacology and Therapeutics, April 1, 2004; 9(2): 129 - 144. [Abstract] [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]
|
|
|
|
|
|
H. Reuter, T. Han, C. Motter, K. D. Philipson, and J. I. Goldhaber Mice overexpressing the cardiac sodium-calcium exchanger: defects in excitation-contraction coupling J. Physiol., February 1, 2004; 554(3): 779 - 789. [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]
|
|
|
|
|
|
M. B. Thomsen, P. G. A. Volders, M. Stengl, R. L. H. M. G. Spaatjens, J. D. M. Beekman, U. Bischoff, M. A. Kall, K. Frederiksen, J. Matz, and M. A. Vos Electrophysiological Safety of Sertindole in Dogs with Normal and Remodeled Hearts J. Pharmacol. Exp. Ther., November 1, 2003; 307(2): 776 - 784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kogler, O. Hartmann, K. Leineweber, P. Nguyen van, P. Schott, O.-E. Brodde, and G. Hasenfuss Mechanical Load-Dependent Regulation of Gene Expression in Monocrotaline-Induced Right Ventricular Hypertrophy in the Rat Circ. Res., August 8, 2003; 93(3): 230 - 237. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Armoundas, I. A. Hobai, G. F. Tomaselli, R. L. Winslow, and B. O'Rourke Role of Sodium-Calcium Exchanger in Modulating the Action Potential of Ventricular Myocytes From Normal and Failing Hearts Circ. Res., July 11, 2003; 93(1): 46 - 53. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Brette and C. Orchard T-Tubule Function in Mammalian Cardiac Myocytes Circ. Res., June 13, 2003; 92(11): 1182 - 1192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. K. Reddy, S. Wasson, S. K.G. Koshy, and R. Komatireddy Structural correlates of electrical remodeling in ventricular hypertrophy Cardiovasc Res, June 1, 2003; 58(3): 495 - 497. [Full Text] [PDF]
|
|
|
|
|
|
M. Peschar, K. Vernooy, W. Y.R Vanagt, R. S Reneman, M. A Vos, and F. W Prinzen Absence of reverse electrical remodeling during regression of volume overload hypertrophy in canine ventricles Cardiovasc Res, June 1, 2003; 58(3): 510 - 517. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M Pogwizd, K. R Sipido, F. Verdonck, and D. M Bers Intracellular Na in animal models of hypertrophy and heart failure: contractile function and arrhythmogenesis Cardiovasc Res, March 15, 2003; 57(4): 887 - 896. [Full Text] [PDF]
|
|
|
|
|
|
W. Schillinger, J. W Fiolet, K. Schlotthauer, and G. Hasenfuss Relevance of Na+-Ca2+ exchange in heart failure Cardiovasc Res, March 15, 2003; 57(4): 921 - 933. [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]
|
|
|
|
|
|
W Schillinger, A Ohler, S Emami, F Muller, C Christians, P.M.L Janssen, H Kogler, N Teucher, B Pieske, T Seidler, et al. The functional effect of adenoviral Na+/Ca2+ exchanger overexpression in rabbit myocytes depends on the activity of the Na+/K+-ATPase Cardiovasc Res, March 15, 2003; 57(4): 996 - 1003. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Verdonck, P. G.A Volders, M. A Vos, and K. R Sipido Increased Na+ concentration and altered Na/K pump activity in hypertrophied canine ventricular cells Cardiovasc Res, March 15, 2003; 57(4): 1035 - 1043. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C Ramakers, M.A Vos, P.A Doevendans, M Schoenmakers, Y.S Wu, S Scicchitano, A Iodice, G.P Thomas, C Antzelevitch, and R Dumaine Coordinated down-regulation of KCNQ1 and KCNE1 expression contributes to reduction of IKs in canine hypertrophied hearts Cardiovasc Res, February 1, 2003; 57(2): 486 - 496. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Sah, R. J Ramirez, G. Y Oudit, D. Gidrewicz, M. G Trivieri, C. Zobel, and P. H Backx Regulation of cardiac excitation-contraction coupling by action potential repolarization: role of the transient outward potassium current (Ito) J. Physiol., January 1, 2003; 546(1): 5 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Gomez, B. Schwaller, H. Porzig, G. Vassort, E. Niggli, and M. Egger Increased Exchange Current but Normal Ca2+ Transport via Na+-Ca2+ Exchange During Cardiac Hypertrophy After Myocardial Infarction Circ. Res., August 23, 2002; 91(4): 323 - 330. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Schillinger, H. Schneider, K. Minami, R. Ferrari, and G. Hasenfuss Importance of sympathetic activation for the expression of Na+-Ca2+ exchanger in end-stage failing human myocardium Eur. Heart J., July 2, 2002; 23(14): 1118 - 1124. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R Sipido, P. G.A Volders, M. A Vos, and F. Verdonck Altered Na/Ca exchange activity in cardiac hypertrophy and heart failure: a new target for therapy? Cardiovasc Res, March 1, 2002; 53(4): 782 - 805. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-X. Yan, S. J. Rials, Y. Wu, T. Liu, X. Xu, R. A. Marinchak, and P. R. Kowey Ventricular hypertrophy amplifies transmural repolarization dispersion and induces early afterdepolarization Am J Physiol Heart Circ Physiol, November 1, 2001; 281(5): H1968 - H1975. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Verduyn, C. Ramakers, G. Snoep, J. D. M. Leunissen, H. J. J. Wellens, and M. A. Vos Time course of structural adaptations in chronic AV block dogs: evidence for differential ventricular remodeling Am J Physiol Heart Circ Physiol, June 1, 2001; 280(6): H2882 - H2890. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.M van Opstal, S.C Verduyn, H.D.M Leunissen, S.H.M de Groot, H.J.J Wellens, and M.A Vos Electrophysiological parameters indicative of sudden cardiac death in the dog with chronic complete AV-block Cardiovasc Res, May 1, 2001; 50(2): 354 - 361. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. Sipido Local Ca2+ Release in Heart Failure : Timing Is Important Circ. Res., November 24, 2000; 87(11): 966 - 968. [Full Text] [PDF]
|
|
|
|
|
|
S. H. M. de Groot, M. Schoenmakers, M. M. C. Molenschot, J. D. M. Leunissen, H. J. J. Wellens, and M. A. Vos Contractile Adaptations Preserving Cardiac Output Predispose the Hypertrophied Canine Heart to Delayed Afterdepolarization-Dependent Ventricular Arrhythmias Circulation, October 24, 2000; 102(17): 2145 - 2151. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Wang, B. Nolan, W. Kutschke, and J. A. Hill Na+-Ca2+ Exchanger Remodeling in Pressure Overload Cardiac Hypertrophy J. Biol. Chem., May 18, 2001; 276(21): 17706 - 17711. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Pogwizd, K. Schlotthauer, L. Li, W. Yuan, and D. M. Bers Arrhythmogenesis and Contractile Dysfunction in Heart Failure : Roles of Sodium-Calcium Exchange, Inward Rectifier Potassium Current, and Residual {beta}-Adrenergic Responsiveness Circ. Res., June 8, 2001; 88(11): 1159 - 1167. [Abstract] [Full Text] [PDF]
|
|