Titin/connectin-based modulation of the Frank-Starling mechanism of the heart

Abstract The basis of the Frank-Starling mechanism of the heart is the increase in active force when muscle is stretched. Various findings have shown that muscle length, i.e., sarcomere length (SL), modulates activation of cardiac myofilaments at a given concentration of $ Ca^{2+} $ ([$ Ca^{2+} $])....
Ausführliche Beschreibung

Abstract The basis of the Frank-Starling mechanism of the heart is the increase in active force when muscle is stretched. Various findings have shown that muscle length, i.e., sarcomere length (SL), modulates activation of cardiac myofilaments at a given concentration of $ Ca^{2+} $ ([$ Ca^{2+} $]). This augmented $ Ca^{2+} $ activation with SL, commonly known as “length-dependent activation”, is manifested as the leftward shift of the force-pCa (=−log [$ Ca^{2+} $]) relation as well as by the increase in maximal $ Ca^{2+} $-activated force. Despite the numerous studies that have been undertaken, the molecular mechanism(s) of length-dependent activation is (are) still not fully understood. The giant sarcomere protein titin/connectin is the largest protein known to date. Titin/connectin is responsible for most passive force in vertebrate striated muscle and also functions as a molecular scaffold during myofibrillogenesis. Recent studies suggest that titin/connectin plays an important role in length-dependent activation by sensing stretch and promoting actomyosin interaction. Here we review and extend this previous work and focus on the mechanism by which titin/connectin might modulate actomyosin interaction. Ausführliche Beschreibung