© 1999 American Heart Association, Inc.
Original Contribution |
Correlation Between Myofilament Response to Ca2+ and Altered Dynamics of Contraction and Relaxation in Transgenic Cardiac Cells That Express ß-Tropomyosin
From the Departments of Physiology and Biophysics (B.M.W., R.S.K., C.C.E., K.A.P., R.M.P., P.P.d.T., R.J.S.) and Medicine, Section of Cardiology (B.M.W.), College of Medicine, University of Illinois at Chicago, Chicago, Ill; and the Department of Molecular Genetics, Biochemistry and Microbiology (M.M., J.O., D.F.W.), College of Medicine, University of Cincinnati, Cincinnati, Ohio. The current address for M. Muthuchamy is Department of Medical Physiology, Texas A&M University Health Science Center, College Station, Tex.
Correspondence to Beata M. Wolska, PhD, Department of Medicine, Section of Cardiology, College of Medicine (M/C 787), University of Illinois at Chicago, 840 S Wood St, Chicago, IL 60612-7323. E-mail bwolska{at}uic.edu
Abstract—We compared the dynamics of the contraction and relaxation of single myocytes isolated from nontransgenic (NTG) mouse hearts and from transgenic (TG-ß-Tm) mouse hearts that overexpress the skeletal isoform of tropomyosin (Tm). Compared with NTG controls, TG-ß-Tm myocytes showed significantly reduced maximal rates of contraction and relaxation with no change in the extent of shortening. This result indicated that the depression in contraction dynamics determined in TG-ß-Tm isolated hearts is intrinsic to the cells. To further investigate the effect of Tm isoform switching on myofilament activity and regulation, we measured myofilament force and ATPase rate as functions of pCa (-log of [Ca2+]). Compared with controls, force generated by myofilaments from TG-ß-Tm hearts and myofibrillar ATPase activity were both more sensitive to Ca2+. However, the shift in pCa50 (half-maximally activating pCa) caused by changing sarcomere length from 1.8 to 2.4 µm was not significantly different between NTG and TG-ß-Tm fiber preparations. To test directly whether isoform switching affected the economy of contraction, force versus ATPase rate relationships were measured in detergent-extracted fiber bundles. In both NTG and TG-ß-Tm preparations, force and ATPase rate were linear and identically correlated, which indicated that crossbridge turnover was unaffected by Tm isoform switching. However, detergent extracted fibers from TG-ß-Tm demonstrated significantly less maximum tension and ATPase activity than NTG controls. Our results provide the first evidence that the Tm isoform population modulates the dynamics of contraction and relaxation of single myocytes by a mechanism that does not alter the rate-limiting step of crossbridge detachment. Our results also indicate that differences in sarcomere-length dependence of activation between cardiac and skeletal muscle are not likely due to differences in the isoform population of Tm.
Key Words: transgenic mice • myocyte • tropomyosin • sarcomere • thin filament
This article has been cited by other articles:
 |
|
 |
|
  G. Jagatheesan, S. Rajan, E. M. Schulz, R. P. H. Ahmed, N. Petrashevskaya, A. Schwartz, G. P. Boivin, G. M. Arteaga, T. Wang, Y.-G. Wang, et al. An internal domain of {beta}-tropomyosin increases myofilament Ca2+ sensitivity Am J Physiol Heart Circ Physiol, July 1, 2009; 297(1): H181 - H190. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ochala, M. Li, M. Ohlsson, A. Oldfors, and L. Larsson Defective regulation of contractile function in muscle fibres carrying an E41K {beta}-tropomyosin mutation J. Physiol., June 15, 2008; 586(12): 2993 - 3004. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Jagatheesan, S. Rajan, N. Petrashevskaya, A. Schwartz, G. Boivin, G. M. Arteaga, R. John Solaro, S. B. Liggett, and D. F. Wieczorek Rescue of tropomyosin-induced familial hypertrophic cardiomyopathy mice by transgenesis Am J Physiol Heart Circ Physiol, August 1, 2007; 293(2): H949 - H958. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Rajan, R. P.H. Ahmed, G. Jagatheesan, N. Petrashevskaya, G. P. Boivin, D. Urboniene, G. M. Arteaga, B. M. Wolska, R. J. Solaro, S. B. Liggett, et al. Dilated Cardiomyopathy Mutant Tropomyosin Mice Develop Cardiac Dysfunction With Significantly Decreased Fractional Shortening and Myofilament Calcium Sensitivity Circ. Res., July 20, 2007; 101(2): 205 - 214. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Ochala, M. Li, H. Tajsharghi, E. Kimber, M. Tulinius, A. Oldfors, and L. Larsson Effects of a R133W beta-tropomyosin mutation on regulation of muscle contraction in single human muscle fibres J. Physiol., June 15, 2007; 581(3): 1283 - 1292. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Vahebi, A. Ota, M. Li, C. M. Warren, P. P. de Tombe, Y. Wang, and R. J. Solaro p38-MAPK Induced Dephosphorylation of {alpha}-Tropomyosin Is Associated With Depression of Myocardial Sarcomeric Tension and ATPase Activity Circ. Res., February 16, 2007; 100(3): 408 - 415. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. L. Engel, T. Kobayashi, B. Biesiadecki, J. Davis, S. Tikunova, S. Wu, and R. J. Solaro Identification of a Region of Troponin I Important in Signaling Cross-bridge-dependent Activation of Cardiac Myofilaments J. Biol. Chem., January 5, 2007; 282(1): 183 - 193. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Gaffin, K. Gokulan, J. C. Sacchettini, T. E. Hewett, R. Klevitsky, J. Robbins, V. Sarin, D. C. Zawieja, G. A. Meininger, and M. Muthuchamy Changes in end-to-end interactions of tropomyosin affect mouse cardiac muscle dynamics Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H552 - H563. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Szczesna-Cordary, G. Guzman, J. Zhao, O. Hernandez, J. Wei, and Z. Diaz-Perez The E22K mutation of myosin RLC that causes familial hypertrophic cardiomyopathy increases calcium sensitivity of force and ATPase in transgenic mice J. Cell Sci., August 15, 2005; 118(16): 3675 - 3683. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D Gaffin, C. W Tong, D. C Zawieja, T. E Hewett, R. Klevitsky, J. Robbins, and M. Muthuchamy Charged residue alterations in the inner-core domain and carboxy-terminus of {alpha}-tropomyosin differentially affect mouse cardiac muscle contractility J. Physiol., December 15, 2004; 561(3): 777 - 791. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Jagatheesan, S. Rajan, N. Petrashevskaya, A. Schwartz, G. Boivin, G. Arteaga, P. P. de Tombe, R. J. Solaro, and D. F. Wieczorek Physiological significance of troponin T binding domains in striated muscle tropomyosin Am J Physiol Heart Circ Physiol, October 1, 2004; 287(4): H1484 - H1494. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Moss, M. Razumova, and D. P. Fitzsimons Myosin Crossbridge Activation of Cardiac Thin Filaments: Implications for Myocardial Function in Health and Disease Circ. Res., May 28, 2004; 94(10): 1290 - 1300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Gaffin, K. Gokulan, J. C. Sacchettini, T. Hewett, R. Klevitsky, J. Robbins, and M. Muthuchamy Charged residue changes in the carboxy-terminus of {alpha}-tropomyosin alter mouse cardiac muscle contractility J. Physiol., April 15, 2004; 556(2): 531 - 543. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. McMullen, T. Shioi, W.-Y. Huang, L. Zhang, O. Tarnavski, E. Bisping, M. Schinke, S. Kong, M. C. Sherwood, J. Brown, et al. The Insulin-like Growth Factor 1 Receptor Induces Physiological Heart Growth via the Phosphoinositide 3-Kinase(p110{alpha}) Pathway J. Biol. Chem., February 6, 2004; 279(6): 4782 - 4793. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Marston and C. S. Redwood Modulation of Thin Filament Activation by Breakdown or Isoform Switching of Thin Filament Proteins: Physiological and Pathological Implications Circ. Res., December 12, 2003; 93(12): 1170 - 1178. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Jagatheesan, S. Rajan, N. Petrashevskaya, A. Schwartz, G. Boivin, S. Vahebi, P. DeTombe, R. J. Solaro, E. Labitzke, G. Hilliard, et al. Functional Importance of the Carboxyl-terminal Region of Striated Muscle Tropomyosin J. Biol. Chem., June 13, 2003; 278(25): 23204 - 23211. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. Diffee, E. A. Seversen, T. D. Stein, and J. A. Johnson Microarray expression analysis of effects of exercise training: increase in atrial MLC-1 in rat ventricles Am J Physiol Heart Circ Physiol, March 1, 2003; 284(3): H830 - H837. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Pieples, G. Arteaga, R. J. Solaro, I. Grupp, J. N. Lorenz, G. P. Boivin, G. Jagatheesan, E. Labitzke, P. P. deTombe, J. P. Konhilas, et al. Tropomyosin 3 expression leads to hypercontractility and attenuates myofilament length-dependent Ca2+ activation Am J Physiol Heart Circ Physiol, October 1, 2002; 283(4): H1344 - H1353. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. F. Martin, R. M. Phillips, A. Kumar, K. Crawford, Z. Abbas, J. L. Lessard, P. de Tombe, and R. J. Solaro Ca2+ activation and tension cost in myofilaments from mouse hearts ectopically expressing enteric gamma -actin Am J Physiol Heart Circ Physiol, August 1, 2002; 283(2): H642 - H649. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Wolska, G. M. Arteaga, J. R. Pena, G. Nowak, R. M. Phillips, S. Sahai, P. P. de Tombe, A. F. Martin, E. G. Kranias, and R. J. Solaro Expression of Slow Skeletal Troponin I in Hearts of Phospholamban Knockout Mice Alters the Relaxant Effect of {beta}-Adrenergic Stimulation Circ. Res., May 3, 2002; 90(8): 882 - 888. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. MacGowan, C. Du, D. F. Wieczorek, and A. P. Koretsky Compensatory changes in Ca2+ and myocardial O2 consumption in beta -tropomyosin transgenic hearts Am J Physiol Heart Circ Physiol, December 1, 2001; 281(6): H2539 - H2548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M Wolska, K. Vijayan, G. M Arteaga, J. P Konhilas, R. M Phillips, R. Kim, T. Naya, J. M Leiden, A. F Martin, P. P de Tombe, et al. Expression of slow skeletal troponin I in adult transgenic mouse heart muscle reduces the force decline observed during acidic conditions J. Physiol., November 1, 2001; 536(3): 863 - 870. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Patel, D. P. Fitzsimons, S. H. Buck, M. Muthuchamy, D. F. Wieczorek, and R. L. Moss PKA accelerates rate of force development in murine skinned myocardium expressing {alpha}- or {beta}-tropomyosin Am J Physiol Heart Circ Physiol, June 1, 2001; 280(6): H2732 - H2739. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Huang, B. M. Wolska, D. E. Montgomery, E. M. Burkart, P. M. Buttrick, and R. J. Solaro Increased contractility and altered Ca2+ transients of mouse heart myocytes conditionally expressing PKC{beta} Am J Physiol Cell Physiol, May 1, 2001; 280(5): C1114 - C1120. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Keller, S.-Y. Shai, C. J. Babbitt, C. G. Pham, R. J. Solaro, M. L. Valencik, J. C. Loftus, and R. S. Ross Disruption of Integrin Function in the Murine Myocardium Leads to Perinatal Lethality, Fibrosis, and Abnormal Cardiac Performance Am. J. Pathol., March 1, 2001; 158(3): 1079 - 1090. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Chandra, V. L. M. Rundell, J. C. Tardiff, L. A. Leinwand, P. P. de Tombe, and R. J. Solaro Ca2+ activation of myofilaments from transgenic mouse hearts expressing R92Q mutant cardiac troponin T Am J Physiol Heart Circ Physiol, February 1, 2001; 280(2): H705 - H713. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. P Fitzsimons, J. R Patel, and R. L Moss Cross-bridge interaction kinetics in rat myocardium are accelerated by strong binding of myosin to the thin filament J. Physiol., January 15, 2001; 530(2): 263 - 272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. C. Evans, J. R. Pena, R. M. Phillips, M. Muthuchamy, D. F. Wieczorek, R. J. Solaro, and B. M. Wolska Altered hemodynamics in transgenic mice harboring mutant tropomyosin linked to hypertrophic cardiomyopathy Am J Physiol Heart Circ Physiol, November 1, 2000; 279(5): H2414 - H2423. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M Arteaga, K. A Palmiter, J. M Leiden, and R J. Solaro Attenuation of length dependence of calcium activation in myofilaments of transgenic mouse hearts expressing slow skeletal troponin I J. Physiol., August 1, 2000; 526(3): 541 - 549. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Moss and J. S.’A. Periera Enhanced Myosin Function Due to a Point Mutation Causing a Familial Hypertrophic Cardiomyopathy Circ. Res., April 14, 2000; 86(7): 720 - 722. [Full Text] [PDF]
|
|
|
|
|
|
R. L. Moss Plasticity in the Dynamics of Myocardial Contraction : Ca2+, Crossbridge Kinetics, or Molecular Cooperation Circ. Res., April 16, 1999; 84(7): 862 - 865. [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]
|
|
|
|
|
|
B. M. Wolska, G. M. Arteaga, J. R. Pena, G. Nowak, R. M. Phillips, S. Sahai, P. P. de Tombe, A. F. Martin, E. G. Kranias, and R. J. Solaro Expression of Slow Skeletal Troponin I in Hearts of Phospholamban Knockout Mice Alters the Relaxant Effect of {beta}-Adrenergic Stimulation Circ. Res., May 3, 2002; 90(8): 882 - 888. [Abstract] [Full Text] [PDF]
|
|