Sarcomere length non-uniformities dictate force production along the descending limb of the force–length relation

The force–length relation is one of the most defining features of muscle contraction, and yet a topic of debate in the literature. The sliding filament theory predicts that the force produced by muscle fibres is proportional to the degree of overlap between myosin and actin filaments, producing a linear descending limb of the active force–length relation. However, several studies have shown forces that are larger than predicted, especially at long sarcomere lengths (SLs). Studies have been conducted with muscle fibres, preparations containing thousands of sarcomeres that make measurements of individual SL challenging. The aim of this study was to evaluate force production and sarcomere dynamics in isolated myofibrils and single sarcomeres from the rabbit psoas muscle to enhance our understanding of the theoretically predicted force–length relation. Contractions at varying SLs along the plateau (SL = 2.25–2.39 µm) and the descending limb (SL > 2.39 µm) of the force–length relation were induced in sarcomeres and myofibrils, and different modes of force measurements were used. Our results show that when forces are measured in single sarcomeres, the experimental force–length relation follows theoretical predictions. When forces are measured in myofibrils with large SL dispersions, there is an extension of the plateau and forces elevated above the predicted levels along the descending limb. We also found an increase in SL non-uniformity and slowed rates of force production at long lengths in myofibrils but not in single sarcomere preparations. We conclude that the deviation of the descending limb of the force–length relation is correlated with the degree of SL non-uniformity and slowed force development.

Muscle contraction: Sliding filament history, sarcomere dynamics and the two Huxleys

Despite having all the evidence needed to come to the right conclusions in the middle of the 1800s, it was not until the 1950s that it was realised by two unrelated Huxleys and their collaborators that striated muscle sarcomeres contain overlapping sets of filaments which do not change much in length and which slide past each other when the muscle sarcomere shortens. It then took quite a while to convince others that this was the case, but now the idea of sliding filaments is fundamental to our understanding of how any muscle works. Here a brief overview of the history of the discovery of sliding filaments and the factors that were missed in the 1800s is followed by an analysis of the more recent experiments which have added to the conviction that all muscles operate on the same guiding principles; two sets of sliding filaments, independent force generators and a mechanism of protein rowing that makes the filaments slide.

Nano-imaging of the beating mouse heart in vivo: Importance of sarcomere dynamics, as opposed to sarcomere length per se, in the regulation of cardiac function

Sarcomeric contraction in cardiomyocytes serves as the basis for the heart’s pump functions in mammals. Although it plays a critical role in the circulatory system, myocardial sarcomere length (SL) change has not been directly measured in vivo under physiological conditions because of technical difficulties. In this study, we developed a high speed (100–frames per second), high resolution (20-nm) imaging system for myocardial sarcomeres in living mice. Using this system, we conducted three-dimensional analysis of sarcomere dynamics in left ventricular myocytes during the cardiac cycle, simultaneously with electrocardiogram and left ventricular pressure measurements. We found that (a) the working range of SL was on the shorter end of the resting distribution, and (b) the left ventricular–developed pressure was positively correlated with the SL change between diastole and systole. The present findings provide the first direct evidence for the tight coupling of sarcomere dynamics and ventricular pump functions in the physiology of the heart.