AJP - Heart Calcium Transients and Cell-Sarcomere
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol 287: H91-H99, 2004. First published March 4, 2004; doi:10.1152/ajpheart.01015.2003
0363-6135/04 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
287/1/H91    most recent
01015.2003v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (11)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Palmer, B. M.
Right arrow Articles by Maughan, D. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Palmer, B. M.
Right arrow Articles by Maughan, D. W.

Differential cross-bridge kinetics of FHC myosin mutations R403Q and R453C in heterozygous mouse myocardium

Bradley M. Palmer,1 David E. Fishbaugher,1 Joachim P. Schmitt,2 Yuan Wang,1 Norman R. Alpert,1 Christine E. Seidman,2 J. G. Seidman,2 Peter VanBuren,1 and David W. Maughan1

1Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, Vermont 05405; and 2Department of Genetics, Howard Hughes Medical Institute and Harvard Medical School, Boston, Massachusetts 02115

Submitted 28 October 2003 ; accepted in final form 21 February 2004

The kinetic effects of the cardiac myosin point mutations R403Q and R453C, which underlie lethal forms of familial hypertrophic cardiomyopathy (FHC), were assessed using isolated myosin and skinned strips taken from heterozygous (R403Q/+ and R453C/+) male mouse hearts. Compared with wild-type (WT) mice, actin-activated ATPase was increased by 38% in R403Q/+ and reduced by 45% in R453C/+, maximal velocity of regulated thin filament (VRTF) in the in vitro motility assay was increased by 8% in R403Q/+ and was not different in R453C/+, myosin concentration at half-maximal VRTF was reduced by 30% in R403Q/+ and not different in R453C/+, and the characteristic frequency for oscillatory work production (b frequency), determined by sinusoidal analysis in the skinned strip at maximal calcium activation, was 27% lower in R403Q/+ and 18% higher in R453C/+. The calcium sensitivity for isometric tension in the skinned strip was not different in R403Q/+ (pCa50 5.64 ± 0.02) and significantly enhanced in R453C/+ (5.82 ± 0.03) compared with WT (5.58 ± 0.02). We conclude that isolated myosin and skinned strips of R403Q/+ and R453C/+ myocardium show marked differences in cross-bridge kinetic parameters and in calcium sensitivity of force production that indicate different functional roles associated with the location of each point mutation at the molecular level.

myosin heavy chain; ATPase; myosin motility; isometric tension; sinusoidal analysis


Address for reprint requests and other correspondence: B. M. Palmer, 127 HSRF Beaumont Ave., Dept. of Molecular Physiology and Biophysics, Univ. of Vermont, Burlington, VT 05405 (E-mail: palmer{at}physiology.med.uvm.edu).




This article has been cited by other articles:


Home page
 Physiol. Rev.Home page
J. Davis, M. V. Westfall, D. Townsend, M. Blankinship, T. J. Herron, G. Guerrero-Serna, W. Wang, E. Devaney, and J. M. Metzger
Designing Heart Performance by Gene Transfer
Physiol Rev, October 1, 2008; 88(4): 1567 - 1651.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
B. M. Palmer, Y. Wang, P. Teekakirikul, J. T. Hinson, D. Fatkin, S. Strouse, P. VanBuren, C. E. Seidman, J. G. Seidman, and D. W. Maughan
Myofilament mechanical performance is enhanced by R403Q myosin in mouse myocardium independent of sex
Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1939 - H1947.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
B. M. Palmer, T. Suzuki, Y. Wang, W. D. Barnes, M. S. Miller, and D. W. Maughan
Two-State Model of Acto-Myosin Attachment-Detachment Predicts C-Process of Sinusoidal Analysis
Biophys. J., August 1, 2007; 93(3): 760 - 769.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
E. P. Debold, J. P. Schmitt, J. B. Patlak, S. E. Beck, J. R. Moore, J. G. Seidman, C. Seidman, and D. M. Warshaw
Hypertrophic and dilated cardiomyopathy mutations differentially affect the molecular force generation of mouse {alpha}-cardiac myosin in the laser trap assay
Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H284 - H291.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
P. Richard, E. Villard, P. Charron, and R. Isnard
The Genetic Bases of Cardiomyopathies
J. Am. Coll. Cardiol., October 27, 2006; 48(9_Suppl_A): A79 - A89.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
S. E. Kirschner, E. Becker, M. Antognozzi, H.-P. Kubis, A. Francino, F. Navarro-Lopez, N. Bit-Avragim, A. Perrot, M. M. Mirrakhimov, K.-J. Osterziel, et al.
Hypertrophic cardiomyopathy-related {beta}-myosin mutations cause highly variable calcium sensitivity with functional imbalances among individual muscle cells
Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1242 - H1251.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2004 by the American Physiological Society.