(Circulation. 1997;95:2312-2317.)
© 1997 American Heart Association, Inc.
Articles |
Decreased Myocyte Tension Development and Calcium Responsiveness in Rat Right Ventricular Pressure Overload
From the Section on Cardiology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1045.
Correspondence to Pieter P. de Tombe, PhD, Department of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago, 900 S Ashland Ave, Chicago, IL 60607-7171. E-mail PDETOMBE{at}UIC.EDU
Background The contractile dysfunction observed in end-stage myocardial hypertrophy has at its base an abnormality in myocyte function. However, whether depressed contractile function is related to an alteration in contractile protein function is presently unknown.
Methods and Results Contractile force, tension, and calcium responsiveness were measured in single-skinned myocytes isolated from rats with right ventricular hypertrophy (RVH) and control rats. RVH was induced by pulmonary artery constriction for 36 weeks and was associated with significant myocyte hypertrophy. Myocytes were attached to micropipettes that extended from a force transducer and motor. Isometric force was measured over a wide range of calcium concentrations at two sarcomere lengths (SLs). Maximal force was increased in the RVH group: 1.20±0.10 versus 1.62±0.13 mg at SL=2.0 µm and 1.33±0.10 versus 1.84±0.15 mg at SL=2.3 µm (P<.05). Maximal tension, however, was reduced in the RVH group: 24.3±1.91 versus 37.5±2.92 mN/mm2 at SL=2.0 µm and 27.4±1.78 versus 41.8±3.19 mN/mm2 at SL=2.3 µm (P<.01). The concentration of calcium ions required for half-maximal activation was increased in the RVH group: 2.64±0.13 versus 3.47±0.22 µmol/L at SL=2.0 µm and 2.23±0.15 versus 2.86±0.18 µmol/L at SL=2.3 µm (P<.01). The slope of the force-calcium relationship (Hill coefficient) was decreased in the RVH group at SL=2.0 µm (4.3±0.4 versus 3.1±0.2, P=.04) but not at SL=2.3 µm (3.8±0.2 versus 3.6±0.2, P=NS).
Conclusions These results suggest that the depressed cardiac function of end-stage myocardial hypertrophy may be due, in part, to altered contractile protein function.
Key Words: heart failure • hypertrophy • contractility • proteins • calcium
This article has been cited by other articles:
 |
|
 |
|
  T. Bupha-Intr, K. M. Haizlip, and P. M. L. Janssen Temporal changes in expression of connexin 43 after load-induced hypertrophy in vitro Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H806 - H814. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Colson, T. Bekyarova, M. R. Locher, D. P. Fitzsimons, T. C. Irving, and R. L. Moss Protein Kinase A-Mediated Phosphorylation of cMyBP-C Increases Proximity of Myosin Heads to Actin in Resting Myocardium Circ. Res., August 1, 2008; 103(3): 244 - 251. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Hamdani, V. Kooij, S. van Dijk, D. Merkus, W. J. Paulus, C. d. Remedios, D. J. Duncker, G. J.M. Stienen, and J. van der Velden Sarcomeric dysfunction in heart failure Cardiovasc Res, March 1, 2008; 77(4): 649 - 658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Belin, M. P. Sumandea, E. J. Allen, K. Schoenfelt, H. Wang, R. J. Solaro, and P. P. de Tombe Augmented Protein Kinase C-{alpha}-Induced Myofilament Protein Phosphorylation Contributes to Myofilament Dysfunction in Experimental Congestive Heart Failure Circ. Res., July 20, 2007; 101(2): 195 - 204. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. F. Edes, D. Czuriga, G. Csanyi, S. Chlopicki, F. A. Recchia, A. Borbely, Z. Galajda, I. Edes, J. van der Velden, G. J. M. Stienen, et al. Rate of tension redevelopment is not modulated by sarcomere length in permeabilized human, murine, and porcine cardiomyocytes Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R20 - R29. [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]
|
|
|
|
|
|
R. J. Belin, M. P. Sumandea, T. Kobayashi, L. A. Walker, V. L. Rundell, D. Urboniene, M. Yuzhakova, S. H. Ruch, D. L. Geenen, R. J. Solaro, et al. Left ventricular myofilament dysfunction in rat experimental hypertrophy and congestive heart failure Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2344 - H2353. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. E. Jweied, R. D. McKinney, L. A. Walker, I. Brodsky, A. S. Geha, M. G. Massad, P. M. Buttrick, and P. P. de Tombe Depressed cardiac myofilament function in human diabetes mellitus Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2478 - H2483. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Borbely, A. Toth, I. Edes, L. Virag, J. G. Papp, A. Varro, W. J. Paulus, J. van der Velden, G. J.M. Stienen, and Z. Papp Peroxynitrite-induced {alpha}-actinin nitration and contractile alterations in isolated human myocardial cells Cardiovasc Res, August 1, 2005; 67(2): 225 - 233. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. E. Gillis, B. Liang, F. Chung, and G. F. Tibbits Increasing mammalian cardiomyocyte contractility with residues identified in trout troponin C Physiol Genomics, June 16, 2005; 22(1): 1 - 7. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Versluis, J. W. Heslinga, P. Sipkema, and N. Westerhof Contractile reserve but not tension is reduced in monocrotaline-induced right ventricular hypertrophy Am J Physiol Heart Circ Physiol, March 1, 2004; 286(3): H979 - H984. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ke, L. Wang, W. G. Pyle, P. P. de Tombe, and R. J. Solaro Intracellular Localization and Functional Effects of P21-Activated Kinase-1 (Pak1) in Cardiac Myocytes Circ. Res., February 6, 2004; 94(2): 194 - 200. [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]
|
|
|
|
 |
|
 J. P Konhilas, T. C Irving, B. M Wolska, E. E Jweied, A. F Martin, R John Solaro, and P. P de Tombe Troponin I in the murine myocardium: influence on length-dependent activation and interfilament spacing J. Physiol., March 15, 2003; 547(3): 951 - 961. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Papp, A. Szabo, J. P. Barends, and G J M Stienen The mechanism of the force enhancement by MgADP under simulated ischaemic conditions in rat cardiac myocytes J. Physiol., August 15, 2002; 543(1): 177 - 189. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. van der Velden, L.J. Klein, R. Zaremba, N.M. Boontje, M.A.J.M. Huybregts, W. Stooker, L. Eijsman, J.W. de Jong, C.A. Visser, F.C. Visser, et al. Effects of Calcium, Inorganic Phosphate, and pH on Isometric Force in Single Skinned Cardiomyocytes From Donor and Failing Human Hearts Circulation, September 4, 2001; 104(10): 1140 - 1146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Suematsu, S. Satoh, S. Kinugawa, H. Tsutsui, S. Hayashidani, R. Nakamura, K. Egashira, N. Makino, and A. Takeshita {alpha}1-Adrenoceptor-Gq-RhoA signaling is upregulated to increase myofibrillar Ca2+ sensitivity in failing hearts Am J Physiol Heart Circ Physiol, August 1, 2001; 281(2): H637 - H646. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. C. Irving, J. Konhilas, D. Perry, R. Fischetti, and P. P. de Tombe Myofilament lattice spacing as a function of sarcomere length in isolated rat myocardium Am J Physiol Heart Circ Physiol, November 1, 2000; 279(5): H2568 - H2573. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. van der Velden, J.W. de Jong, V.J. Owen, P.B.J. Burton, and G.J.M. Stienen Effect of protein kinase A on calcium sensitivity of force and its sarcomere length dependence in human cardiomyocytes Cardiovasc Res, June 1, 2000; 46(3): 487 - 495. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Papp, J. van der Velden, and G.J.M Stienen Calpain-I induced alterations in the cytoskeletal structure and impaired mechanical properties of single myocytes of rat heart Cardiovasc Res, March 1, 2000; 45(4): 981 - 993. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. E. G. Ekelund, R. W. Harrison, O. Shokek, R. N. Thakkar, R. S. Tunin, H. Senzaki, D. A. Kass, E. Marban, and J. M. Hare Intravenous Allopurinol Decreases Myocardial Oxygen Consumption and Increases Mechanical Efficiency in Dogs With Pacing-Induced Heart Failure Circ. Res., September 3, 1999; 85(5): 437 - 445. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J van der Velden, L.J Klein, M van der Bijl, M.A.J.M Huybregts, W Stooker, J Witkop, L Eijsman, C.A Visser, F.C Visser, and G.J.M Stienen Isometric tension development and its calcium sensitivity in skinned myocyte-sized preparations from different regions of the human heart Cardiovasc Res, June 1, 1999; 42(3): 706 - 719. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. G. Perez, K. Hashimoto, S. McCune, R. A. Altschuld, and E. Marban Origin of Contractile Dysfunction in Heart Failure : Calcium Cycling Versus Myofilaments Circulation, March 2, 1999; 99(8): 1077 - 1083. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J van der Velden, L.J Klein, M van der Bijl, M.A.J.M Huybregts, W Stooker, J Witkop, L Eijsman, C.A Visser, F.C Visser, and G.J.M Stienen Force production in mechanically isolated cardiac myocytes from human ventricular muscle tissue Cardiovasc Res, May 1, 1998; 38(2): 414 - 423. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. P de Tombe Altered contractile function in heart failure Cardiovasc Res, February 1, 1998; 37(2): 367 - 380. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. P. Dobesh, J. P. Konhilas, and P. P. de Tombe Cooperative activation in cardiac muscle: impact of sarcomere length Am J Physiol Heart Circ Physiol, March 1, 2002; 282(3): H1055 - H1062. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Cazorla, Y. Wu, T. C. Irving, and H. Granzier Titin-Based Modulation of Calcium Sensitivity of Active Tension in Mouse Skinned Cardiac Myocytes Circ. Res., May 25, 2001; 88(10): 1028 - 1035. [Abstract] [Full Text] [PDF]
|
|