© 1997 American Heart Association, Inc.
Articles |
Enhanced Na+-Ca2+ Exchange in the Infarcted Heart
Implications for Excitation-Contraction Coupling
From the Division of Cardiology, Salt Lake City Veterans Affairs Medical Center (S.E.L.), the Nora Eccles Harrison Cardiovascular Research and Training Institute (S.E.L., J.H.B.B.), and the University of Utah (S.E.L., J.H.B.B.), Salt Lake City.
Correspondence to Sheldon E. Litwin, MD, Cardiovascular Division, Veterans Affairs Medical Center, 500 Foothill Blvd, Salt Lake City, UT 84148. E-mail SLitwin{at}msscc.med.utah.edu
Abstract Cellular Ca2+ regulation is abnormal in diseased hearts. We designed this study to assess the role of the Na+-Ca2+ exchanger in excitation-contraction coupling in surviving myocardium of the infarcted heart. We measured cellular contractions and whole-cell currents in single left ventricular myocytes isolated from the hearts of rabbits with healed myocardial infarction (MI). Eight weeks after MI, rabbits had left ventricular dysfunction without overt heart failure. Myocytes isolated from regions adjacent to the infarcted zone were significantly longer than cells from control hearts. At low stimulation rates (0.5 Hz), the amplitude of field-stimulated contractions was increased (11.6±0.5% versus 10.2±0.6% resting cell length), whereas the time to peak shortening and action potential duration were prolonged in the MI cells. When stimulation frequency was increased to 2.0 Hz, cellular shortening did not change or decreased in myocytes from infarcted hearts, whereas control cells had a positive shortening-interval relationship. Cells from infarcted hearts had a significantly decreased (31%) L-type Ca2+ current (ICa) density but no change in the current-voltage relationship or the kinetics of ICa inactivation. Maximal Na+-Ca2+ exchange current density was significantly increased (32%) in the cells from infarcted hearts. Sarcoplasmic reticulum (SR) Ca2+ content during a stable train of contractions, as estimated from caffeine-induced inward currents, was slightly increased (P=NS) in the MI myocytes. To determine whether Na+-Ca2+ exchange influenced SR Ca2+ content, cells were clamped at potentials between -70 and +90 mV for 400 ms. The amplitude of the contraction during a subsequent clamp step to +10 mV was then measured as an index of SR loading that occurred during the preceding clamp step. Steps to positive potentials produced greater augmentation of the subsequent contraction in MI than in control myocytes. In myocytes from the infarcted heart, increased activity of the Na+-Ca2+ exchanger may promote Ca2+ entry or decrease Ca2+ extrusion. This relative augmentation of inward Ca2+ flux by the exchanger may enhance SR Ca2+ loading and thus support contractility that would otherwise be impaired as a result of decreased Ca2+ current. However, Ca2+ influx by the exchanger may contribute to the prolongation of contractions in myocytes from infarcted hearts.
Key Words: myocardial infarction • Ca2+ • ion channel • Na+-Ca2+ exchange • heart failure
This article has been cited by other articles:
 |
|
 |
|
  A. E. Belevych, D. Terentyev, S. Viatchenko-Karpinski, R. Terentyeva, A. Sridhar, Y. Nishijima, L. D. Wilson, A. J. Cardounel, K. R. Laurita, C. A. Carnes, et al. Redox modification of ryanodine receptors underlies calcium alternans in a canine model of sudden cardiac death Cardiovasc Res, December 1, 2009; 84(3): 387 - 395. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Chandrasekaran, R. E. Peterson, S. K. Mani, B. Addy, A. L. Buchholz, L. Xu, T. Thiyagarajan, H. Kasiganesan, C. B. Kern, and D. R. Menick Histone deacetylases facilitate sodium/calcium exchanger up-regulation in adult cardiomyocytes FASEB J, November 1, 2009; 23(11): 3851 - 3864. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Xu, C. S. Kappler, S. K. Mani, N. R. Shepherd, L. Renaud, P. Snider, S. J. Conway, and D. R. Menick Chronic Administration of KB-R7943 Induces Up-regulation of Cardiac NCX1 J. Biol. Chem., October 2, 2009; 284(40): 27265 - 27272. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Wang, T. O. Chan, X.-Q. Zhang, E. Gao, J. Song, W. J. Koch, A. M. Feldman, and J. Y. Cheung Induced overexpression of Na+/Ca2+ exchanger transgene: altered myocyte contractility, [Ca2+]i transients, SR Ca2+ contents, and action potential duration Am J Physiol Heart Circ Physiol, August 1, 2009; 297(2): H590 - H601. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. N. Sharikabad, J. M. Aronsen, E. Haugen, J. Pedersen, A.-S. W. Moller, H. K. Mork, H. C. D. Aass, O. M. Sejersted, I. Sjaastad, and O. Brors Cardiomyocytes from postinfarction failing rat hearts have improved ischemia tolerance Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H787 - H795. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. R. Heinzel, V. Bito, L. Biesmans, M. Wu, E. Detre, F. von Wegner, P. Claus, S. Dymarkowski, F. Maes, J. Bogaert, et al. Remodeling of T-Tubules and Reduced Synchrony of Ca2+ Release in Myocytes From Chronically Ischemic Myocardium Circ. Res., February 15, 2008; 102(3): 338 - 346. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Smith Matters of the heart: the physiology of cardiac function and failure Exp Physiol, November 1, 2007; 92(6): 973 - 986. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. G. Daniels, T. Naya, V. L. M. Rundell, and P. P. de Tombe Development of contractile dysfunction in rat heart failure: hierarchy of cellular events Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R284 - R292. [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]
|
|
|
|
|
|
A. A. Armoundas, J. Rose, R. Aggarwal, B. D. Stuyvers, B. O'Rourke, D. A. Kass, E. Marban, S. R. Shorofsky, G. F. Tomaselli, and C. William Balke Cellular and molecular determinants of altered Ca2+ handling in the failing rabbit heart: primary defects in SR Ca2+ uptake and release mechanisms Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1607 - H1618. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Wasserstrom and G. L. Aistrup Digitalis: new actions for an old drug Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H1781 - H1793. [Abstract] [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]
|
|
|
|
|
|
S. Saba, A. M. Janczewski, L. C. Baker, V. Shusterman, E. C. Gursoy, A. M. Feldman, G. Salama, C. F. McTiernan, and B. London Atrial contractile dysfunction, fibrosis, and arrhythmias in a mouse model of cardiomyopathy secondary to cardiac-specific overexpression of tumor necrosis factor-{alpha} Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1456 - H1467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Dun, S. Baba, T. Yagi, and P. A. Boyden Dynamic remodeling of K+ and Ca2+ currents in cells that survived in the epicardial border zone of canine healed infarcted heart Am J Physiol Heart Circ Physiol, September 1, 2004; 287(3): H1046 - H1054. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Song, X.-Q. Zhang, J. Wang, L. L. Carl, B. A. Ahlers, L. I. Rothblum, and J. Y. Cheung Sprint training improves contractility in postinfarction rat myocytes: role of Na+/Ca2+ exchange J Appl Physiol, August 1, 2004; 97(2): 484 - 490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Yatani, S.-J. Kim, R. K. Kudej, Q. Wang, C. Depre, K. Irie, E. G. Kranias, S. F. Vatner, and D. E. Vatner Insights into cardioprotection obtained from study of cellular Ca2+ handling in myocardium of true hibernating mammals Am J Physiol Heart Circ Physiol, June 1, 2004; 286(6): H2219 - H2228. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. F. Rossow, E. Minami, E. G. Chase, C. E. Murry, and L.F. Santana NFATc3-Induced Reductions in Voltage-Gated K+ Currents After Myocardial Infarction Circ. Res., May 28, 2004; 94(10): 1340 - 1350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Heusch and K. R. Sipido Myocardial Hibernation: A Double-Edged Sword Circ. Res., April 30, 2004; 94(8): 1005 - 1007. [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]
|
|
|
|
 |
|
 F R Quinn, S Currie, A M Duncan, S Miller, R Sayeed, S M Cobbe, and G L Smith Myocardial infarction causes increased expression but decreased activity of the myocardial Na+--Ca2+ exchanger in the rabbit J. Physiol., November 15, 2003; 553(1): 229 - 242. [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
I. Sjaastad, J A. Wasserstrom, and O. M Sejersted Heart failure - a challenge to our current concepts of excitation-contraction coupling J. Physiol., January 1, 2003; 546(1): 33 - 47. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-Q. Zhang, J. Song, A. Qureshi, L. I. Rothblum, L. L. Carl, Q. Tian, and J. Y. Cheung Rescue of contractile abnormalities by Na+/Ca2+ exchanger overexpression in postinfarction rat myocytes J Appl Physiol, December 1, 2002; 93(6): 1925 - 1931. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-Y. Min, M. F. Sullivan, X. Yan, X. Feng, V. Chu, J.-F. Wang, I. Amende, J. P. Morgan, K. D. Philipson, and T. G. Hampton Overexpression of Na+/Ca2+ exchanger gene attenuates postinfarction myocardial dysfunction Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2466 - H2471. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Sjaastad, J. Bokenes, F. Swift, J. A. Wasserstrom, and O. M. Sejersted Normal contractions triggered by ICa,L in ventricular myocytes from rats with postinfarction CHF Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H1225 - H1236. [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
R. Sah, R. J. Ramirez, and P. H. Backx Modulation of Ca2+ Release in Cardiac Myocytes by Changes in Repolarization Rate: Role of Phase-1 Action Potential Repolarization in Excitation-Contraction Coupling Circ. Res., February 8, 2002; 90(2): 165 - 173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. An, S. G. Varadarajan, A. Camara, Q. Chen, E. Novalija, G. J. Gross, and D. F. Stowe Blocking Na+/H+ exchange reduces [Na+]i and [Ca2+]i load after ischemia and improves function in intact hearts Am J Physiol Heart Circ Physiol, December 1, 2001; 281(6): H2398 - H2409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. G. Daniels, R. S. Keller, and P. P. de Tombe Losartan prevents contractile dysfunction in rat myocardium after left ventricular myocardial infarction Am J Physiol Heart Circ Physiol, November 1, 2001; 281(5): H2150 - H2158. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Meszaros, D. Khananshvili, and G. Hart Mechanisms underlying delayed afterdepolarizations in hypertrophied left ventricular myocytes of rats Am J Physiol Heart Circ Physiol, August 1, 2001; 281(2): H903 - H914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Sah, R. J Ramirez, R. Kaprielian, and P. H Backx Alterations in action potential profile enhance excitation-contraction coupling in rat cardiac myocytes J. Physiol., May 15, 2001; 533(1): 201 - 214. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Shigekawa and T. Iwamoto Cardiac Na+-Ca2+ Exchange : Molecular and Pharmacological Aspects Circ. Res., May 11, 2001; 88(9): 864 - 876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-Q. Zhang, L.-Q. Zhang, B. M. Palmer, Y.-C. Ng, T. I. Musch, R. L. Moore, and J. Y. Cheung Sprint training shortens prolonged action potential duration in postinfarction rat myocyte: mechanisms J Appl Physiol, May 1, 2001; 90(5): 1720 - 1728. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. L Burton and S. M Cobbe Dispersion of ventricular repolarization and refractory period Cardiovasc Res, April 1, 2001; 50(1): 10 - 23. [Full Text] [PDF]
|
|
|
|
|
|
S. G. Varadarajan, J. An, E. Novalija, S. C. Smart, and D. F. Stowe Changes in [Na+]i, compartmental [Ca2+], and NADH with dysfunction after global ischemia in intact hearts Am J Physiol Heart Circ Physiol, January 1, 2001; 280(1): H280 - H293. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. G. Hampton, J.-F. Wang, J. DeAngelis, I. Amende, K. D. Philipson, and J. P. Morgan Enhanced gene expression of Na+/Ca2+ exchanger attenuates ischemic and hypoxic contractile dysfunction Am J Physiol Heart Circ Physiol, December 1, 2000; 279(6): H2846 - H2854. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Heerdt, J. W. Holmes, B. Cai, A. Barbone, J. D. Madigan, S. Reiken, D. L. Lee, M. C. Oz, A. R. Marks, and D. Burkhoff Chronic Unloading by Left Ventricular Assist Device Reverses Contractile Dysfunction and Alters Gene Expression in End-Stage Heart Failure Circulation, November 28, 2000; 102(22): 2713 - 2719. [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. E. Litwin, D. Zhang, and J. H. B. Bridge Dyssynchronous Ca2+ Sparks in Myocytes From Infarcted Hearts Circ. Res., November 24, 2000; 87(11): 1040 - 1047. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. Sipido, P. G. A. Volders, S. H. M. de Groot, F. Verdonck, F. Van de Werf, H. J. J. Wellens, and M. A. Vos Enhanced Ca2+ Release and Na/Ca Exchange Activity in Hypertrophied Canine Ventricular Myocytes : Potential Link Between Contractile Adaptation and Arrhythmogenesis Circulation, October 24, 2000; 102(17): 2137 - 2144. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Pogwizd Increased Na+-Ca2+ Exchanger in the Failing Heart Circ. Res., October 13, 2000; 87(8): 641 - 643. [Full Text] [PDF]
|
|
|
|
|
|
I. A. Hobai and B. O'Rourke Enhanced Ca2+-Activated Na+-Ca2+ Exchange Activity in Canine Pacing-Induced Heart Failure Circ. Res., October 13, 2000; 87(8): 690 - 698. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Gupta, A. J.C Prahash, and I. S Anand Myocyte contractile function is intact in the post-infarct remodeled rat heart despite molecular alterations Cardiovasc Res, October 1, 2000; 48(1): 77 - 88. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. H. Barry Na+-Ca2+ Exchange in Failing Myocardium : Friend or Foe? Circ. Res., September 29, 2000; 87(7): 529 - 531. [Full Text] [PDF]
|
|
|
|
|
|
L.-Q. Zhang, X.-Q. Zhang, T. I. Musch, R. L. Moore, and J. Y. Cheung Sprint training restores normal contractility in postinfarction rat myocytes J Appl Physiol, September 1, 2000; 89(3): 1099 - 1105. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Wasserstrom, E. Holt, I. Sjaastad, P. K. Lunde, A. Odegaard, and O. M. Sejersted Altered E-C coupling in rat ventricular myocytes from failing hearts 6 wk after MI Am J Physiol Heart Circ Physiol, August 1, 2000; 279(2): H798 - H807. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-Q. Zhang, X.-Q. Zhang, Y.-C. Ng, L. I. Rothblum, T. I. Musch, R. L. Moore, and J. Y. Cheung Sprint training normalizes Ca2+ transients and SR function in postinfarction rat myocytes J Appl Physiol, July 1, 2000; 89(1): 38 - 46. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mitarai, T. D. Reed, and A. Yatani Changes in ionic currents and beta -adrenergic receptor signaling in hypertrophied myocytes overexpressing Galpha q Am J Physiol Heart Circ Physiol, July 1, 2000; 279(1): H139 - H148. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. C Knollmann, B. E C Knollmann-Ritschel, N. J Weissman, L. R Jones, and M. Morad Remodelling of ionic currents in hypertrophied and failing hearts of transgenic mice overexpressing calsequestrin J. Physiol., June 1, 2000; 525(2): 483 - 498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Wickenden, R. Kaprielian, X.-M. You, and P. H. Backx The thyroid hormone analog DITPA restores Ito in rats after myocardial infarction Am J Physiol Heart Circ Physiol, April 1, 2000; 278(4): H1105 - H1116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. L. Riemer and L. Tung Focal extracellular potential: a means to monitor electrical activity in single cardiac myocytes Am J Physiol Heart Circ Physiol, April 1, 2000; 278(4): H1383 - H1394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Litwin, D. Zhang, P. Roberge, and G. D. Pennock DITPA prevents the blunted contraction-frequency relationship in myocytes from infarcted hearts Am J Physiol Heart Circ Physiol, March 1, 2000; 278(3): H862 - H870. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.A. McIntosh, S.M. Cobbe, and G.L. Smith Heterogeneous changes in action potential and intracellular Ca2+ in left ventricular myocyte sub-types from rabbits with heart failure Cardiovasc Res, January 14, 2000; 45(2): 397 - 409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-Q. Zhang, Y.-C. Ng, R. L. Moore, T. I. Musch, and J. Y. Cheung In situ SR function in postinfarction myocytes J Appl Physiol, December 1, 1999; 87(6): 2143 - 2150. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Pogwizd, M. Qi, W. Yuan, A. M. Samarel, and D. M. Bers Upregulation of Na+/Ca2+ Exchanger Expression and Function in an Arrhythmogenic Rabbit Model of Heart Failure Circ. Res., November 26, 1999; 85(11): 1009 - 1019. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Blaustein and W. J. Lederer Sodium/Calcium Exchange: Its Physiological Implications Physiol Rev, July 1, 1999; 79(3): 763 - 854. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M.B Pinto and P. A Boyden Electrical remodeling in ischemia and infarction Cardiovasc Res, May 1, 1999; 42(2): 284 - 297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-Q. Zhang, T. I. Musch, R. Zelis, and J. Y. Cheung Effects of impaired Ca2+ homeostasis on contraction in postinfarction myocytes J Appl Physiol, March 1, 1999; 86(3): 943 - 950. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Sah, R. J. Ramirez, and P. H. Backx Modulation of Ca2+ Release in Cardiac Myocytes by Changes in Repolarization Rate: Role of Phase-1 Action Potential Repolarization in Excitation-Contraction Coupling Circ. Res., February 8, 2002; 90(2): 165 - 173. [Abstract] [Full Text] [PDF]
|
|