Effect of troponin C on the cooperativity in Ca²⁺ activation of cardiac muscle

Abstract

This study describes the effects of exchanging native cardiac troponin C (CTnC) from the right ventricular muscle of Syrian hamster for purified skeletal (S) TnC from fast twitch muscles in triggering cardiac contraction.Ca2+ sensitivity of the myocardium became decreased with STnC to 62% of the original value with CTnC. Furthermore, the slope of the pCa-force curve of cardiac muscle was found to be increased with STnC. The results show that the TnC moiety, as part of the switching mechanism during activation, also regulates thin-filament cooperativity in muscle. Modifications in both the Ca2+ sensitivity and cooperativity are associated with alterations in the primary structure of TnC.

Substitution of cardiac troponin C into rabbit muscle does not alter the length dependence of Ca2+ sensitivity of tension.

“…The pCa50 for one fibre (Fig. 3) (Moss et al 1986;Gulati, Scordilis & Babu, 1988) showed that partial replacement of endogenous sTnC in skeletal muscle fibres resulted in a decrease in the steepness of the tension-pCa relationship at lengths corresponding to the long lengths in this study. The apparent lack of effect of cTnC on steepness in the present study is presumably due to the fact that the small number of data points required to describe the mid-region of the tension-pCa relationship was insufficient to accurately characterize the slope of either phase of a Hill plot.…”

The role of troponin C in the length dependence of Ca(2+)‐sensitive force of mammalian skeletal and cardiac muscles.

“…(1) Cardiac TnC Sr21 sensitivity has previously been demonstrated to be 5-to 6-fold greater than that of skeletal TnC (Babu et al 1987. (2) The skeletal TnC Hill coefficient for the pCa-force relation has previously been demonstrated to be higher than that manifest by cardiac TnC, indicating greater co-operativity in the skeletal Ca2+-activation mechanism (Moss et al 1986;Gulati, Scordilis & Babu, 1988 Babu et al 1987;their Fig. 6).…”

Molecular cloning and expression of chicken cardiac troponin C.

“…When Sr 2+ is used as the divalent cation, the replacement of cardiac TnC in the heart with the skeletal isoform changes the relative cooperativity of cardiac muscle to a pattern observed in skeletal muscle. 12 In addition, recent evidence suggests that replacement of cardiac TnC in the heart with the fast skeletal isoform alters force generation in cardiac muscle under calcium control 13 and that TnC may be a basis for Starling's law of the heart. 33 Thus, although the atria and ventricles of the heart have the potential The strict regulation of cardiac TnC expression in the heart is in contrast with that observed in fast skeletal muscles in which cardiac and skeletal isoforms are observed. ''…”

“…This is especially important in light of recent physiological data that demonstrate that changing the TnC content of both cardiac and fast skeletal muscles alters the force generation characteristics of striated muscle. 12 - 13 Immunochemical analysis has suggested that embryonic fast skeletal muscles of the chicken and rat express a TnC antigenically similar to the slow/cardiac isoform, whereas the adult muscles are thought to synthesize only TnC recognized by anti-fast skeletal TnC antibodies. 4 -6 In contrast, Bucher et al 14 have recently shown the presence of the slow/cardiac TnC transcript in adult quail pectoralis muscle.…”