Аннотация:Significance The Frank–Starling law of the heart represents a fundamental regulatory mechanism whereby cardiac pump performance is directly modulated by the extent of diastolic ventricular filling on a beat-to-beat basis. It is now well established that sarcomere length (SL)-induced changes in cardiac contractile protein responsiveness to activating calcium ions play a major role in this phenomenon. However, the molecular mechanisms that underlie this SL-sensing property are not known. Here, we show by small-angle X-ray diffraction and fluorescent probe techniques that the giant protein titin likely transmits the length signal to induce structural alterations in both thin- and thick-filament contractile proteins. These findings provide insights into the molecular basis of the Frank–Starling regulatory mechanism.
