Myocardial length-dependent activation, the basis of the Frank-Starling mechanism, is coordinately regulated by sarcomere proteins including titin and troponin.
Titin and troponin coordinately regulate myocardial length-dependent activation, providing a modern molecular understanding of the Frank-Starling mechanism.
The basis of the Frank-Starling mechanism of the heart is the intrinsic ability of cardiac muscle to produce greater active force in response to stretch, a phenomenon known as length-dependent activation. A feedback mechanism transmitted from cross-bridge formation to troponin C to enhance Ca(2+) binding has long been proposed to account for length-dependent activation. However, recent advances in muscle physiology research technologies have enabled the identification of other factors involved in length-dependent activation. The striated muscle sarcomere contains a third filament system composed of the giant elastic protein titin, which is responsible for most passive stiffness in the physiological sarcomere length range. Recent studies have revealed a significant coupling of active and passive forces in cardiac muscle, where titin-based passive force promotes cross-bridge recruitment, resulting in greater active force production in response to stretch. More currently, the focus has been placed on the troponin-based "on-off" switching of the thin filament state in the regulation of length-dependent activation. In this review, we discuss how myocardial length-dependent activation is coordinately regulated by sarcomere proteins.
Fukuda et al. (2009) conducted a review in Myocardial length-dependent activation. Myocardial length-dependent activation, the basis of the Frank-Starling mechanism, is coordinately regulated by sarcomere proteins including titin and troponin.