title: 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 Ca2+ ([Ca2+]). This augmented Ca2+ activation with SL, commonly known as "length-dependent activation", is manifested as the leftward shift of the force-pCa (= -log [Ca2+]) relation as well as by the increase in maximal Ca2+ -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.
authors.affiliation: Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, WA 99164, USA. noriof@jikei.ac
authors.forename: Norio
authors.initials: N
authors.lastname: Fukuda
authors.forename: Henk L
authors.initials: HL
authors.lastname: Granzier
mesh_terms: D000205:Actomyosin / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D064211:Connectin; D006321:Heart / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D009124:Muscle Proteins / Q000502:physiology*; D009200:Myocardial Contraction / Q000502:physiology*; D020033:Protein Isoforms / Q000502:physiology; D011494:Protein Kinases / Q000502:physiology*; D012518:Sarcomeres / Q000502:physiology
chemical_list: D064211:Connectin; D009124:Muscle Proteins; D020033:Protein Isoforms; C577285:TTN protein, human; D000205:Actomyosin; D011494:Protein Kinases; D002118:Calcium