Exchanging beta-tropomyosin for native alpha-tropomyosin in transgenic mouse hearts increased thin filament activation and Ca2+ sensitivity of steady state force.
Despite its potential as a key determinant of the functional state of striated muscle, the impact of tropomyosin (Tm) isoform switching on mammalian myofilament activation and regulation in the intact lattice remains unclear. Using a transgenic approach to specifically exchange beta-Tm for the native alpha-Tm in mouse hearts, we have been able to uncover novel functions of Tm isoform switching in the heart. The myofilaments containing beta-Tm demonstrated an increase in the activation of the thin filament by strongly bound cross-bridges, an increase in Ca2+ sensitivity of steady state force, and a decrease in the rightward shift of the Ca2+-force relation induced by cAMP-dependent phosphorylation. Our results are the first to demonstrate the specific effects of Tm isoform switching on mammalian thin filament activation in the intact lattice and suggest an important role for Tm in modulation of myofilament activity by phosphorylation of troponin.
Palmiter et al. (Wed,) conducted a other in Myofilament activation and regulation. Exchange of beta-tropomyosin for native alpha-tropomyosin vs. Native alpha-tropomyosin was evaluated on Thin filament activation, Ca2+ sensitivity of steady state force, and response to cAMP-dependent phosphorylation. Exchanging beta-tropomyosin for native alpha-tropomyosin in transgenic mouse hearts increased thin filament activation and Ca2+ sensitivity of steady state force.