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

Norio Fukuda, Henk L. Granzier

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)319-323
Number of pages5
JournalJournal of Muscle Research and Cell Motility
Issue number6-8
StatePublished - Dec 2005

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cell Biology


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