Troponin T modulates sarcomere length-dependent recruitment of cross-bridges in cardiac muscle

摘要

The heterogenic nature of troponin T (TnT) isoforms in fast skeletal and cardiac muscle suggests important functional differences. Dynamic features of rat cardiac TnT (cTnT) and rat fast skeletal TnT (fsTnT) reconstituted cardiac muscle preparations were captured by fitting the force response of small amplitude (0.5%) muscle length changes to the recruitment-distortion model. The recruitment of force-bearing cross-bridges (XBs) by increases in muscle length was favored by cTnT. The recruitment magnitude was similar to 1.5 times greater for cTnT-than for fsTnT-reconstituted muscle fibers. The speed of length-mediated XB recruitment (b) in cTnT-reconstituted muscle fiber was 0.50-0.57 times as fast as fsTnT-reconstituted muscle fibers (3.05 vs. 5.32 s(-1) at sarcomere length, SL, of 1.9 mu m and 4.16 vs. 8.36 s(-1) at SL of 2.2 mu m). Due to slowing of b in cTnT-reconstituted muscle fibers, the frequency of minimum stiffness (f(min)) was shifted to lower frequencies of muscle length changes (at SL of 1.9 mu m, 0.64 Hz, and 1.16 Hz for cTnT-and fsTnT-reconstituted muscle fibers, respectively; at SL of 2.2 mu m, 0.79 Hz, and 1.11 Hz for cTnT-and fsTnT-reconstituted muscle fibers, respectively). Our model simulation of the data implicates TnT as a participant in the process by which SL-and XB-regulatory unit cooperative interactions activate thin filaments. Our data suggest that the amino-acid sequence differences in cTnT may confer a heart-specific regulatory role cTnT may participate in tuning the heart muscle by decreasing the speed of XB recruitment so that the heart beats at a rate commensurate with f(min).