| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Department of Molecular Genetics, Biochemistry, and Microbiology, 2 Department of Pharmacology and Cell Biophysics, 3 Department of Molecular and Cellular Physiology, 4 Department of Pathology and Laboratory Medicine, College of Medicine, University of Cincinnati, Cincinnati, Ohio 45267-0529; 5 Department of Physiology and Biophysics, College of Medicine, University of Illinois, Chicago, 60612; and 6 Center for Synchrotron Radiation Research and Instrumentation and Department of Biological, Chemical, and Physical Sciences, Illinois Institute of Technology, Chicago, Illinois 60616
Tropomyosin
(TM), an integral component of the thin filament, is encoded by three
striated muscle isoforms: 
-TM, 
-TM, and TPM 3. Although the
-TM and -TM isoforms are well characterized, less is known about
the function of the TPM 3 isoform, which is predominantly found in the
slow-twitch musculature of mammals. To determine its functional
significance, we ectopically expressed this isoform in the hearts of
transgenic mice. We generated six transgenic mouse lines that produce
varying levels of TPM 3 message with ectopic TPM 3 protein accounting
for 40-60% of the total striated muscle tropomyosin. The
transgenic mice have normal life spans and exhibit no morphological
abnormalities in their sarcomeres or hearts. However, there are
significant functional alterations in cardiac performance.
Physiological assessment of these mice by using closed-chest analyses
and a work-performing model reveals a hyperdynamic effect on systolic
and diastolic function. Analysis of detergent-extracted fiber bundles
demonstrates a decreased sensitivity to Ca2+ in force
generation and a decrease in length-dependent Ca2+
activation with no detectable change in interfilament spacing as
determined by using X-ray diffraction. Our data are the first to
demonstrate that TM isoforms can affect sarcomeric performance by
decreasing sensitivity to Ca2+ and influencing the
length-dependent Ca2+ activation.
heart; cardiac muscle; thin filament regulation
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]
|
|
|
|
 |
|
 D. R. Fermin, A. Barac, S. Lee, S. P. Polster, S. Hannenhalli, T. L. Bergemann, S. Grindle, D. B. Dyke, F. Pagani, L. W. Miller, et al. Sex and Age Dimorphism of Myocardial Gene Expression in Nonischemic Human Heart Failure Circ Cardiovasc Genet, December 1, 2008; 1(2): 117 - 125. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Y. Kostrominova, D. E. Dow, R. G. Dennis, R. A. Miller, and J. A. Faulkner Comparison of gene expression of 2-mo denervated, 2-mo stimulated-denervated, and control rat skeletal muscles Physiol Genomics, July 14, 2005; 22(2): 227 - 243. [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]
|
|
|
|
 |
|
 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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
