EXCHANGE OF BETA-TROPOMYOSIN FOR ALPHA-TROPOMYOSIN IN HEARTS OF TRANSGENIC MICE INDUCES CHANGES IN THIN FILAMENT RESPONSE TO CA2-BRIDGE BINDING, AND PROTEIN-PHOSPHORYLATION( STRONG CROSS)

Despite its potential as a key determinant of the functional state of striated muscle, the impact of tropomyosin (Tm) isoform switching on m ammalian myofilament activation and regulation in the intact lattice r emains unclear. Using a transgenic approach to specifically exchange b eta-Tm for the native alpha-Tm in mouse hearts, we have been able to u ncover novel functions of Tm isoform switching in the heart. The myofi laments containing beta-Tm demonstrated an increase in the activation of the thin filament by strongly bound cross-bridges, an increase in C a2+ sensitivity of steady state force, and a decrease in the rightward shift of the Ca2+-force relation induced by cAMP-dependent phosphoryl ation. Our results are the first to demonstrate the specific effects o f Tm isoform switching on mammalian thin filament activation in the in tact lattice and suggest an important role for Tm in modulation of myo filament activity by phosphorylation of troponin.