Role of the Giant Elastic Protein Titin in the Frank-Starling Mechanism of the Heart
Norio Fukuda and Henk Granzier
Pages 135-139 (5)
Increased ventricular volume enhances the systolic performance, a phenomenon known as Frank-Starlings law of the heart. At its basis is the ability of cardiac muscle to produce increased active force in response to increased muscle length. Although numerous studies have been conducted to elucidate the molecular basis of length-dependent activation, the mechanism remains elusive. The giant protein titin (also known as connectin) is the third filament system in the sarcomere and is responsible for most passive stiffness of striated muscle in the physiological sarcomere length range. The force generated by titin is usually seen as passive and independent of active force generation. Recent findings, however, suggest that titin-based passive force modulates actin-myosin interaction, resulting in greater active force in response to stretch. In this short review, we discuss the molecular mechanisms of length-dependent activation, focusing on the possible role of titin in its regulation.
heart, cardiac muscle, frank-starling, sarcomere length, titin
Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington StateUniversity, Pullman, WA 99164-6520, USA.