Titin and Troponin: Central Players in the Frank-Starling Mechanism of the Heart
Norio Fukuda, Takako Terui, Iwao Ohtsuki, Shin'ichi Ishiwata and Satoshi Kurihara
Pages 119-124 (6)
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 Ca2+ 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 lengthdependent activation is coordinately regulated by sarcomere proteins.
Calcium, cardiac muscle, connectin
Department of Cell Physiology, The Jikei University School of Medicine, 3-25-8 Nishishinbashi, Minato-ku, Tokyo 105-8461, Japan.