The second of two special issues on contractile systems charts further progress towards an understanding of myofilament regulation.
Colson discusses a recent investigation of the functional effect of slow myosin binding protein-C in slow-twitch skeletal muscle fibers.
Chase examines a study using the MUSICO model of striated muscle to evaluate the function of giant elastic proteins titin and nebulin.
Milestones in Physiology
Moss and Solaro recall Bárány’s landmark study that identified myosin ATPase as the fundamental driver of contraction speed.
Investigation into the mechanism of thin filament regulation by transient kinetics and equilibrium binding: Is there a conflict?
The authors examine the apparent discrepancies from studies aimed at understanding the mechanism of thin filament regulation.
The expression of β-myosin heavy chain (β-MHC) in the guinea pig heart increases during postnatal development. Reda et al. show that this increase in β-MHC enhances length-mediated increases in myofilament Ca2+ sensitivity and sarcomere length–dependent changes in contractile function.
Myosin binding protein C (MyBP-C) is thought to regulate the contraction of skeletal muscle. Robinett et al. show that phosphorylation of slow skeletal MyBP-C modulates contraction by recruiting cross-bridges, modifying cross-bridge kinetics, and altering internal drag forces in the C-zone.
Changes in mechanical load, hormones, or metabolic stress provoke remodeling of the actin-based thin filaments within muscle fibers. Solís and Russell show that several signaling pathways converge at the actin-capping protein CapZ to regulate muscle fiber growth in response to mechanical stiffness and neurohumoral signaling.
Enigma Homologue (ENH) is a Z-disc protein whose loss causes cardiomyopathy, but whose function in muscle mechanics is poorly understood. Gregorich et al. show that ENH affects tension redevelopment in mouse myocardium, possibly by altering cross-bridge cycling kinetics or the compliance of the Z-disc.
The contractility of striated muscle can be modulated by various mutations in nebulin and titin present in human disease. Mijailovich et al. perform computational simulations coupled with experimental observations to provide insights into the mechanisms by which mutations in these proteins cause disease phenotypes.