The structure of the native cardiac thin filament at systolic Ca <sup>2+</sup> levels
Cristina M. Risi, Ian Pepper, Betty Belknap, Maicon Landim-Vieira, Howard D. White, Kelly A. Dryden, José R. Pinto, P. Bryant Chase, Vitold E. Galkin
Abstract
Significance Heartbeats rely on cyclical interactions between myosin thick and actin thin filaments orchestrated by rising and falling Ca 2+ . During systole, Ca 2+ binds to the thin filament and allows its interaction with the thick filament to produce force required for contraction. The structure of the thin filament at physiological Ca 2+ levels is unknown, which limits our understanding of the thin filament regulation by Ca 2+ . Here, we directly observe thin filament structural states along individual filaments at systolic Ca 2+ levels to show that the thin filament is activated stochastically with short-range cooperativity evident only on one strand of the thin filament. We suggest how cardiac muscle can be regulated by a narrow range of Ca 2+ levels upon transition from diastole to systole.