|
|
||||||||
1 Department of Clinical
Pharmacology,
Several mutations in human cardiac troponin T (TnT) gene have been reported to cause hypertrophic cardiomyopathy (HCM). To explore the effects of the mutations on cardiac muscle contractile function under physiological conditions, human cardiac TnT mutants, Ile79Asn and Arg92Gln, as well as wild type, were expressed in Escherichia coli and exchanged into permeabilized rabbit cardiac muscle fibers, and Ca2+-activated force was determined. The free Ca2+ concentrations required for tension generation were found to be significantly lower in the mutant TnT-exchanged fibers than in the wild-type TnT-exchanged fibers, whereas no significant differences were found in tension-generating capability under maximal activating conditions and in cooperativity. These results suggest that a heightened Ca2+ sensitivity of cardiac muscle contraction is one of the factors to cause HCM associated with these TnT mutations.
hypertrophy; missense mutation; skinned fibers; calcium sensitivity; heart diseases; ischemia
This article has been cited by other articles:
![]() |
P. Robinson, M. Mirza, A. Knott, H. Abdulrazzak, R. Willott, S. Marston, H. Watkins, and C. Redwood Alterations in Thin Filament Regulation Induced by a Human Cardiac Troponin T Mutant That Causes Dilated Cardiomyopathy Are Distinct from Those Induced by Troponin T Mutants That Cause Hypertrophic Cardiomyopathy J. Biol. Chem., October 18, 2002; 277(43): 40710 - 40716. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Fatkin and R. M. Graham Molecular Mechanisms of Inherited Cardiomyopathies Physiol Rev, October 1, 2002; 82(4): 945 - 980. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. G. Pyle, J. W. Lester, and P. A. Hofmann Effects of {kappa}-opioid receptor activation on myocardium Am J Physiol Heart Circ Physiol, August 1, 2001; 281(2): H669 - H678. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. J. Baker, C. H. Redfern, M. D. Harwood, P. C. Simpson, and B. R. Conklin Abnormal contraction caused by expression of Gi-coupled receptor in transgenic model of dilated cardiomyopathy Am J Physiol Heart Circ Physiol, April 1, 2001; 280(4): H1653 - H1659. [Abstract] [Full Text] [PDF] |
||||
![]() |
O. M. Hernandez, P. R. Housmans, and J. D. Potter Plasticity in Skeletal, Cardiac, and Smooth Muscle: Invited Review: Pathophysiology of cardiac muscle contraction and relaxation as a result of alterations in thin filament regulation J Appl Physiol, March 1, 2001; 90(3): 1125 - 1136. [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] |
||||
![]() |
A. M. Gordon, E. Homsher, and M. Regnier Regulation of Contraction in Striated Muscle Physiol Rev, April 1, 2000; 80(2): 853 - 924. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Szczesna, R. Zhang, J. Zhao, M. Jones, G. Guzman, and J. D. Potter Altered Regulation of Cardiac Muscle Contraction by Troponin T Mutations That Cause Familial Hypertrophic Cardiomyopathy J. Biol. Chem., January 7, 2000; 275(1): 624 - 630. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Nakaura, S. Morimoto, F. Yanaga, M. Nakata, H. Nishi, T. Imaizumi, and I. Ohtsuki Functional changes in troponin T by a splice donor site mutation that causes hypertrophic cardiomyopathy Am J Physiol Cell Physiol, August 1, 1999; 277(2): C225 - C232. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Miller, D. Szczesna, P. R. Housmans, J. Zhao, F. de Freitas, A. V. Gomes, L. Culbreath, J. McCue, Y. Wang, Y. Xu, et al. Abnormal Contractile Function in Transgenic Mice Expressing a Familial Hypertrophic Cardiomyopathy-linked Troponin T (I79N) Mutation J. Biol. Chem., February 2, 2001; 276(6): 3743 - 3755. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Morimoto, Q.-W. Lu, K. Harada, F. Takahashi-Yanaga, R. Minakami, M. Ohta, T. Sasaguri, and I. Ohtsuki Ca2+-desensitizing effect of a deletion mutation Delta K210 in cardiac troponin T that causes familial dilated cardiomyopathy PNAS, January 22, 2002; 99(2): 913 - 918. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |