scholarly journals Cardiac troponin T mutations result in allele-specific phenotypes in a mouse model for hypertrophic cardiomyopathy

1999 ◽  
Vol 104 (4) ◽  
pp. 469-481 ◽  
Author(s):  
Jil C. Tardiff ◽  
Timothy E. Hewett ◽  
Bradley M. Palmer ◽  
Charlotte Olsson ◽  
Stephen M. Factor ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Mouse Model ◽  
Cardiac Troponin ◽  
Troponin T ◽  
Cardiac Troponin T ◽  
Allele Specific

Phenotypic Variation of Familial Hypertrophic Cardiomyopathy Caused by the Phe110→Ile Mutation in Cardiac Troponin T

Cardiology ◽  
2000 ◽  
Vol 93 (3) ◽  
pp. 155-162 ◽  
Author(s):  
Tong-Lang Lin ◽  
Sahoko Ichihara ◽  
Yoshiji Yamada ◽  
Tetsuo Nagasaka ◽  
Hitoshi Ishihara ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Phenotypic Variation ◽  
Cardiac Troponin ◽  
Troponin T ◽  
Familial Hypertrophic Cardiomyopathy ◽  
Cardiac Troponin T

scholarly journals Hypertrophic cardiomyopathy mutation in cardiac troponin T (R95H) attenuates length-dependent activation in guinea pig cardiac muscle fibers

2017 ◽  
Vol 313 (6) ◽  
pp. H1180-H1189 ◽  
Author(s):  
Alexis V. Mickelson ◽  
Murali Chandra
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Guinea Pig ◽  
Central Region ◽  
Cardiac Troponin ◽  
Sarcomere Length ◽  
Troponin T ◽  
Cardiac Troponin T ◽  
Cross Bridge ◽  
Cardiac Muscle Fibers ◽  
Length Dependent Activation

The central region of cardiac troponin T (TnT) is important for modulating the dynamics of muscle length-mediated cross-bridge recruitment. Therefore, hypertrophic cardiomyopathy mutations in the central region may affect cross-bridge recruitment dynamics to alter myofilament Ca2+ sensitivity and length-dependent activation of cardiac myofilaments. Given the importance of the central region of TnT for cardiac contractile dynamics, we studied if hypertrophic cardiomyopathy-linked mutation (TnTR94H)-induced effects on contractile function would be differently modulated by sarcomere length (SL). Recombinant wild-type TnT (TnTWT) and the guinea pig analog of the human R94H mutation (TnTR95H) were reconstituted into detergent-skinned cardiac muscle fibers from guinea pigs. Steady-state and dynamic contractile measurements were made at short and long SLs (1.9 and 2.3 µm, respectively). Our results demonstrated that TnTR95H increased pCa50 (−log of free Ca2+ concentration) to a greater extent at short SL; TnTR95H increased pCa50 by 0.11 pCa units at short SL and 0.07 pCa units at long SL. The increase in pCa50 associated with an increase in SL from 1.9 to 2.3 µm (ΔpCa50) was attenuated nearly twofold in TnTR95H fibers; ΔpCa50 was 0.09 pCa units for TnTWT fibers but only 0.05 pCa units for TnTR95H fibers. The SL dependency of rate constants of cross-bridge distortion dynamics and tension redevelopment was also blunted by TnTR95H. Collectively, our observations on the SL dependency of pCa50 and rate constants of cross-bridge distortion dynamics and tension redevelopment suggest that mechanisms underlying the length-dependent activation cardiac myofilaments are attenuated by TnTR95H. NEW & NOTEWORTHY Mutant cardiac troponin T (TnTR95H) differently affects myofilament Ca2+ sensitivity at short and long sarcomere length, indicating that mechanisms underlying length-dependent activation are altered by TnTR95H. TnTR95H enhances myofilament Ca2+ sensitivity to a greater extent at short sarcomere length, thus attenuating the length-dependent increase in myofilament Ca2+ sensitivity.

Plasma cardiac troponin T closely correlates with infarct size in a mouse model of acute myocardial infarction

2002 ◽  
Vol 325 (1-2) ◽  
pp. 87-90 ◽  
Author(s):  
Bernhard Metzler ◽  
Angelika Hammerer-Lercher ◽  
Johannes Jehle ◽  
Hermann Dietrich ◽  
Otmar Pachinger ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Mouse Model ◽  
Infarct Size ◽  
Cardiac Troponin ◽  
Troponin T ◽  
Cardiac Troponin T
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