Fast skeletal muscle troponin T increases the cooperativity of transgenic mouse cardiac muscle contraction

1. To investigate the functional significance of different troponin T (TnT) isoforms in the Ca²⁺ activation of muscle contraction, transgenic mice have been constructed with a chicken fast skeletal muscle TnT transgene driven by a cardiac α-myosin heavy chain gene promoter. Cardiac muscle-specific expression of the fast skeletal muscle TnT has been obtained with significant myofibril incorporation. Expression of the endogenous cardiac muscle thin filament regulatory proteins, such as troponin I and tropomyosin, was not altered in the transgenic mouse heart, providing an authentic system for the functional characterization of TnT isoforms. 3. Cardiac muscle coatractility was analysed for the force vs. Ca²⁺ relationship in skinned ventricular trabeculae of transgenic mice in comparison with wild-type litter-mates. The results showed unchanged pCa₅₀ values (5.1 ± 0.04 and 5.1 ± 0.1, respectively) but significantly steeper slopes (the Hill coefficient was 2.0 ± 0.2 vs. 1.0 ± 0.2, P < 0.05). 4. The results demonstrate that the structural and functional variation of different TnT isoforms may contribute to the difference in responsiveness and overall cooperativity of the thin filament-based Ca²⁺ regulation between cardiac and skeletal muscles.