Journal
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume 280, Issue 2, Pages H705-H713Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.2001.280.2.H705
Keywords
skinned fiber bundles; contraction; calcium sensitivity; crossbridge cycling; rate constant of tension redevelopment
Funding
- NHLBI NIH HHS [HL-53222, P01 HL-62426, R37 HL-22231] Funding Source: Medline
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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 Ca2+ than nontransgenic (NTG) fibers [negative logarithm of half maximally activating molar Ca2+ (pCa(50)) = 5.84 +/- 0.01 and 6.12 +/- 0.01 for NTG and TG fibers, respectively]. The shift in pCa50 caused by increasing the sarcomere length from 1.9 to 2.3 mum was significantly higher for TG than for NTG fibers (Delta pCa(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 Ca2+ 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 Ca2+ sensitivity in TG myofilaments.
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