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Ca2 activation of myofilaments from tran ... R92Q mutant cardiac troponin T
Ca(2+) activation of myofilaments from transgenic mouse hearts expressing R92Q mutant cardiac troponin T.
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The functional consequences of the R92Q mutation in cardiac troponin T (cTnT), linked to familial hypertrophic cardiomyopathy in humans, are not well understood. We have studied steady- and pre-steady-state mechanical activity of detergent-skinned fiber bundles from a transgenic (TG) mouse model in which 67% of the total cTnT in the heart was replaced by the R92Q mutant cTnT. TG fibers were more sensitive to Ca(2+) than nontransgenic (NTG) fibers [negative logarithm of half maximally activating molar Ca(2+) (pCa(50)) = 5.84 +/- 0.01 and 6.12 +/- 0.01 for NTG and TG fibers, respectively]. The shift in pCa(50) caused by increasing the sarcomere length from 1.9 to 2.3 microm was significantly higher for TG than for NTG fibers (DeltapCa(50) = 0.13 +/- 0.01 and 0.29 +/- 0.02 for NTG and TG fibers, respectively). The relationships between rate of ATP consumption and steady-state isometric tension were linear, and the slopes were the same in NTG and TG fibers. Rate of tension redevelopment was more sensitive to Ca(2+) in TG than in NTG fibers (pCa(50) = 5.71 +/- 0.02 and 6.07 +/- 0.02 for NTG and TG fibers, respectively). We concluded that overall cross-bridge cycling kinetics are not altered by the R92Q mutation but that altered troponin-tropomyosin interactions could be responsible for the increase in myofilament Ca(2+) sensitivity in TG myofilaments.
Chandra M, Rundell VL, Tardiff JC, Leinwand LA, De Tombe PP, Solaro RJ
American journal of physiology. Heart and circulatory physiology
2001-02-01 00:00
280
2
H705-13
Acidosis,Adenosine Triphosphate,Animals,Calcium,Cross-Linking Reagents,Detergents,Genes, myc,Humans,Mice,Mice, Transgenic,Microfilaments,Muscle Contraction,Muscle Fibers,Mutation,Promoter Regions (Genetics),Troponin T,Cross-Linking Reagents,Detergents,Troponin T,Adenosine Triphosphate,Calcium
Department of Physiology and Biophysics and Cardiovascular Sciences Program, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, USA
Am. J. Physiol. Heart Circ. Physiol.
NHLBI HL-53222, NHLBI P01 HL-62426, NHLBI R37 HL-22231
0363-6135
684
True
11158969
