Regulating Striated Muscle Contraction: Through Thick and Thin

Elisabetta Brunello*, Luca Fusi*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

3 Citations (Scopus)
43 Downloads (Pure)


Force generation in striated muscle is primarily controlled by structural changes in the actin-containing thin filaments triggered by an increase in intracellular calcium concentration. However, recent studies have elucidated a new class of regulatory mechanisms, based on the myosin-containing thick filament, that control the strength and speed of contraction by modulating the availability of myosin motors for the interaction with actin. This review summarizes the mechanisms of thin and thick filament activation that regulate the contractility of skeletal and cardiac muscle. A novel dual-filament paradigm of muscle regulation is emerging, in which the dynamics of force generation depends on the coordinated activation of thin and thick filaments. We highlight the interfilament signaling pathways based on titin and myosin-binding protein-C that couple thin and thick filament regulatory mechanisms. This dual-filament regulation mediates the length-dependent activation of cardiac muscle that underlies the control of the cardiac output in each heartbeat.
Original languageEnglish
Pages (from-to)255-275
Number of pages21
JournalAnnual Review of Physiology
Early online date6 Nov 2023
Publication statusE-pub ahead of print - 6 Nov 2023


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