| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 1999 American Heart Association, Inc.
Original Contribution |
The Sarcoplasmic Reticulum and the Na+/Ca2+ Exchanger Both Contribute to the Ca2+ Transient of Failing Human Ventricular Myocytes
From the Temple University School of Medicine Departments of Physiology (K.D., J.A.M., S.R.H.), Internal Medicine (K.B.M.), and Surgery (V.J.), Philadelphia, Pa.
Correspondence to Steven R. Houser, PhD, Professor of Physiology, Temple University School of Medicine Department of Physiology, 3420 N Broad St, Philadelphia, PA 19140. E-mail srhouser{at}astro.ocis.temple.edu
Abstract—Our objective was to determine the respective roles of the sarcoplasmic reticulum (SR) and the Na+/Ca2+ exchanger in the small, slowly decaying Ca2+ transients of failing human ventricular myocytes. Left ventricular myocytes were isolated from explanted hearts of patients with severe heart failure (n=18). Cytosolic Ca2+, contraction, and action potentials were measured by using indo-1, edge detection, and patch pipettes, respectively. Selective inhibitors of SR Ca2+ transport (thapsigargin) and reverse-mode Na+/Ca2+ exchange activity (No. 7943, Kanebo Ltd) were used to define the respective contribution of these processes to the Ca2+ transient. Ca2+ transients and contractions induced by action potentials (AP transients) at 0.5 Hz exhibited phasic and tonic components. The duration of the tonic component was determined by the action potential duration. Ca2+ transients induced by caffeine (Caf transients) exhibited only a phasic component with a rapid rate of decay that was dependent on extracellular Na+. The SR Ca2+-ATPase inhibitor thapsigargin abolished the phasic component of the AP Ca2+ transient and of the Caf transient but had no significant effect on the tonic component of the AP transient. The Na+/Ca2+ exchange inhibitor No. 7943 eliminated the tonic component of the AP transient and reduced the magnitude of the phasic component. In failing human myocytes, Ca2+ transients and contractions exhibit an SR-related, phasic component and a slow, reverse-mode Na+/Ca2+ exchange–related tonic component. These findings suggest that Ca2+ influx via reverse-mode Na+/Ca2+ exchange during the action potential may contribute to the slow decay of the Ca2+ transient in failing human myocytes.
Key Words: calcium transient • isolated myocyte • heart failure • Na+/Ca2+ exchanger • sarcoplasmic reticulum
This article has been cited by other articles:
 |
|
 |
|
  L. Belardinelli, A. Dhalla, and J. Shryock Abnormal left ventricular relaxation in patients with long QT syndrome Eur. Heart J., November 2, 2009; 30(22): 2813 - 2814. [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]
|
|
|
|
|
|
J. Lee, M. A. Stagg, S. Fukushima, G. K. R. Soppa, U. Siedlecka, S. J. Youssef, K. Suzuki, M. H. Yacoub, and C. M. N. Terracciano Adult progenitor cell transplantation influences contractile performance and calcium handling of recipient cardiomyocytes Am J Physiol Heart Circ Physiol, April 1, 2009; 296(4): H927 - H936. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Cunha, N. Bhasin, and P. J. Mohler Targeting and Stability of Na/Ca Exchanger 1 in Cardiomyocytes Requires Direct Interaction with the Membrane Adaptor Ankyrin-B J. Biol. Chem., February 16, 2007; 282(7): 4875 - 4883. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Eder, D. Probst, C. Rosker, M. Poteser, H. Wolinski, S.D. Kohlwein, C. Romanin, and K. Groschner Phospholipase C-dependent control of cardiac calcium homeostasis involves a TRPC3-NCX1 signaling complex Cardiovasc Res, January 1, 2007; 73(1): 111 - 119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. B. Brunckhorst, I. Shemer, Y. Mika, S. A. Ben-Haim, and D. Burkhoff Cardiac contractility modulation by non-excitatory currents: Studies in isolated cardiac muscle Eur J Heart Fail, January 1, 2006; 8(1): 7 - 15. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. A. Shmist, R. Kamburg, G. Ophir, A. Kozak, V. Shneyvays, Y. J. Appelbaum, and A. Shainberg N,N,N',N'-Tetrakis(2-pyridylmethyl)-ethylenediamine Improves Myocardial Protection against Ischemia by Modulation of Intracellular Ca2+ Homeostasis J. Pharmacol. Exp. Ther., June 1, 2005; 313(3): 1046 - 1057. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Maack, A. Ganesan, A. Sidor, and B. O'Rourke Cardiac Sodium-Calcium Exchanger Is Regulated by Allosteric Calcium and Exchanger Inhibitory Peptide at Distinct Sites Circ. Res., January 7, 2005; 96(1): 91 - 99. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. W. Chaudhary, E. I. Rossman, V. Piacentino III, A. Kenessey, C. Weber, J. P. Gaughan, K. Ojamaa, I. Klein, D. M. Bers, S. R. Houser, et al. Altered myocardial Ca2+ cycling after left ventricular assist device support in the failing human heart J. Am. Coll. Cardiol., August 18, 2004; 44(4): 837 - 845. [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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 M. T. Ziolo, L. S. Maier, V. Piacentino III, J. Bossuyt, S. R. Houser, and D. M. Bers Myocyte Nitric Oxide Synthase 2 Contributes to Blunted {beta}-Adrenergic Response in Failing Human Hearts by Decreasing Ca2+ Transients Circulation, April 20, 2004; 109(15): 1886 - 1891. [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
R. C. Balijepalli, A. J. Lokuta, N. A. Maertz, J. M. Buck, R. A. Haworth, H. H. Valdivia, and T. J. Kamp Depletion of T-tubules and specific subcellular changes in sarcolemmal proteins in tachycardia-induced heart failure Cardiovasc Res, July 1, 2003; 59(1): 67 - 77. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Antoons, M. Ver Heyen, L. Raeymaekers, P. Vangheluwe, F. Wuytack, and K. R. Sipido Ca2+ Uptake by the Sarcoplasmic Reticulum in Ventricular Myocytes of the SERCA2b/b Mouse Is Impaired at Higher Ca2+ Loads Only Circ. Res., May 2, 2003; 92(8): 881 - 887. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-k. Wei, A. Ruknudin, S. U. Hanlon, J. M. McCurley, D. H. Schulze, and M. C.P. Haigney Protein Kinase A Hyperphosphorylation Increases Basal Current but Decreases {beta}-Adrenergic Responsiveness of the Sarcolemmal Na+-Ca2+ Exchanger in Failing Pig Myocytes Circ. Res., May 2, 2003; 92(8): 897 - 903. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Pieske and S. R Houser [Na+]i handling in the failing human heart Cardiovasc Res, March 15, 2003; 57(4): 874 - 886. [Abstract] [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]
|
|
|
|
|
|
S. R. Houser and K. B. Margulies Is Depressed Myocyte Contractility Centrally Involved in Heart Failure? Circ. Res., March 7, 2003; 92(4): 350 - 358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. von Lewinski, K. Voss, S. Hulsmann, H. Kogler, and B. Pieske Insulin-Like Growth Factor-1 Exerts Ca2+-Dependent Positive Inotropic Effects in Failing Human Myocardium Circ. Res., February 7, 2003; 92(2): 169 - 176. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-L. Ward, A. J Pope, D. S Loiselle, and M. B Cannell Reduced contraction strength with increased intracellular [Ca2+] in left ventricular trabeculae from failing rat hearts J. Physiol., January 15, 2003; 546(2): 537 - 550. [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]
|
|
|
|
|
|
K. F Frank, B. Bolck, E. Erdmann, and R. H.G Schwinger Sarcoplasmic reticulum Ca2+-ATPase modulates cardiac contraction and relaxation Cardiovasc Res, January 1, 2003; 57(1): 20 - 27. [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]
|
|
|
|
|
|
M. Petretta, M. L.E. Vicario, L. Spinelli, A. Ferro, A. Cuocolo, M. Condorelli, and D. Bonaduce Combined effect of the force-frequency and length-tension mechanisms on left ventricular function in patients with dilated cardiomyopathy Eur J Heart Fail, December 1, 2002; 4(6): 727 - 735. [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]
|
|
|
|
|
|
M. T. Jiang, A. J. Lokuta, E. F. Farrell, M. R. Wolff, R. A. Haworth, and H. H. Valdivia Abnormal Ca2+ Release, but Normal Ryanodine Receptors, in Canine and Human Heart Failure Circ. Res., November 29, 2002; 91(11): 1015 - 1022. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Chen, V. Piacentino III, S. Furukawa, B. Goldman, K. B. Margulies, and S. R. Houser L-Type Ca2+ Channel Density and Regulation Are Altered in Failing Human Ventricular Myocytes and Recover After Support With Mechanical Assist Devices Circ. Res., September 20, 2002; 91(6): 517 - 524. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Pieske, L. S. Maier, V. Piacentino III, J. Weisser, G. Hasenfuss, and S. Houser Rate Dependence of [Na+]i and Contractility in Nonfailing and Failing Human Myocardium Circulation, July 23, 2002; 106(4): 447 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Despa, M. A. Islam, C. R. Weber, S. M. Pogwizd, and D. M. Bers Intracellular Na+ Concentration Is Elevated in Heart Failure But Na/K Pump Function Is Unchanged Circulation, May 28, 2002; 105(21): 2543 - 2548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Hunton, P. A. Lucchesi, Y. Pang, X. Cheng, L. J. Dell'Italia, and R. B. Marchase Capacitative Calcium Entry Contributes to Nuclear Factor of Activated T-cells Nuclear Translocation and Hypertrophy in Cardiomyocytes J. Biol. Chem., April 12, 2002; 277(16): 14266 - 14273. [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]
|
|
|
|
|
|
J. G. Muller, Y. Isomatsu, S. V. Koushik, M. O'Quinn, L. Xu, C. S. Kappler, E. Hapke, M. R. Zile, S. J. Conway, and D. R. Menick Cardiac-Specific Expression and Hypertrophic Upregulation of the Feline Na+-Ca2+ Exchanger Gene H1-Promoter in a Transgenic Mouse Model Circ. Res., February 8, 2002; 90(2): 158 - 164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. Weber, V. Piacentino III, K. S. Ginsburg, S. R. Houser, and D. M. Bers Na+-Ca2+ Exchange Current and Submembrane [Ca2+] During the Cardiac Action Potential Circ. Res., February 8, 2002; 90(2): 182 - 189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-k. Wei, J. F Quigley, S. U Hanlon, B. O'Rourke, and M. C.P Haigney Cytosolic free magnesium modulates Na/Ca exchange currents in pig myocytes Cardiovasc Res, February 1, 2002; 53(2): 334 - 340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kubo, K. B. Margulies, V. Piacentino III, J. P. Gaughan, and S. R. Houser Patients With End-Stage Congestive Heart Failure Treated With {beta}-Adrenergic Receptor Antagonists Have Improved Ventricular Myocyte Calcium Regulatory Protein Abundance Circulation, August 28, 2001; 104(9): 1012 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J Conway and S. V Koushik Cardiac sodium-calcium exchanger: a double-edged sword Cardiovasc Res, August 1, 2001; 51(2): 194 - 197. [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]
|
|
|
|
|
|
C. M.N. Terracciano, K. D. Philipson, and K. T. MacLeod Overexpression of the Na+/Ca2+ exchanger and inhibition of the sarcoplasmic reticulum Ca2+-ATPase in ventricular myocytes from transgenic mice Cardiovasc Res, January 1, 2001; 49(1): 38 - 47. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ruknudin, S. He, W J Lederer, and D. H Schulze Functional differences between cardiac and renal isoforms of the rat Na+-Ca2+ exchanger NCX1 expressed in Xenopus oocytes J. Physiol., December 15, 2000; 529(3): 599 - 610. [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]
|
|
|
|
 |
|
 L. Hove-Madsen, A. Llach, and L. Tort Na+/Ca2+-exchange activity regulates contraction and SR Ca2+ content in rainbow trout atrial myocytes Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2000; 279(5): R1856 - R1864. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M.N Terracciano Sarcoplasmic reticulum calcium release function and FK binding proteins in heart failure: another piece of a complex jigsaw Cardiovasc Res, November 1, 2000; 48(2): 191 - 193. [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]
|
|
|
|
|
|
W. H. Barry Na+-Ca2+ Exchange in Failing Myocardium : Friend or Foe? Circ. Res., September 29, 2000; 87(7): 529 - 531. [Full Text] [PDF]
|
|
|
|
|
|
W. Schillinger, P. M. L. Janssen, S. Emami, S. A. Henderson, R. S. Ross, N. Teucher, O. Zeitz, K. D. Philipson, J. Prestle, and G. Hasenfuss Impaired Contractile Performance of Cultured Rabbit Ventricular Myocytes After Adenoviral Gene Transfer of Na+-Ca2+ Exchanger Circ. Res., September 29, 2000; 87(7): 581 - 587. [Abstract] [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]
|
|
|
|
|
|
P. G.A. Volders, M. A. Vos, B. Szabo, K. R. Sipido, S.H.M. de Groot, A. P.M. Gorgels, H. J.J. Wellens, and R. Lazzara Progress in the understanding of cardiac early afterdepolarizations and torsades de pointes: time to revise current concepts Cardiovasc Res, June 1, 2000; 46(3): 376 - 392. [Full Text] [PDF]
|
|
|
|
|
|
W. H. Barry Molecular Inotropy : A Future Approach to the Treatment of Heart Failure? Circulation, December 7, 1999; 100(23): 2303 - 2304. [Full Text] [PDF]
|
|
|
|
|
|
J. I. Goldhaber Sodium-Calcium Exchange : The Phantom Menace Circ. Res., November 26, 1999; 85(11): 982 - 984. [Full Text] [PDF]
|
|
|
|
|
|
Y. Ji, M. J. Lalli, G. J. Babu, Y. Xu, D. L. Kirkpatrick, L. H. Liu, N. Chiamvimonvat, R. A. Walsh, G. E. Shull, and M. Periasamy Disruption of a Single Copy of the SERCA2 Gene Results in Altered Ca2+ Homeostasis and Cardiomyocyte Function J. Biol. Chem., November 22, 2000; 275(48): 38073 - 38080. [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]
|
|
|
|
|
|
J. G. Muller, Y. Isomatsu, S. V. Koushik, M. O'Quinn, L. Xu, C. S. Kappler, E. Hapke, M. R. Zile, S. J. Conway, and D. R. Menick Cardiac-Specific Expression and Hypertrophic Upregulation of the Feline Na+-Ca2+ Exchanger Gene H1-Promoter in a Transgenic Mouse Model Circ. Res., February 8, 2002; 90(2): 158 - 164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. Weber, V. Piacentino III, K. S. Ginsburg, S. R. Houser, and D. M. Bers Na+-Ca2+ Exchange Current and Submembrane [Ca2+] During the Cardiac Action Potential Circ. Res., February 8, 2002; 90(2): 182 - 189. [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]
|
|
|
|
|
|
M. Jane Lalli, J. Yong, V. Prasad, K. Hashimoto, D. Plank, G. J. Babu, D. Kirkpatrick, R. A. Walsh, M. Sussman, A. Yatani, et al. Sarcoplasmic Reticulum Ca2+ ATPase (SERCA) 1a Structurally Substitutes for SERCA2a in the Cardiac Sarcoplasmic Reticulum and Increases Cardiac Ca2+ Handling Capacity Circ. Res., July 20, 2001; 89(2): 160 - 167. [Abstract] [Full Text] [PDF]
|
|