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.

Force enhancement after stretch of isolated myofibrils is increased by sarcomere length non-uniformities.

When a muscle is stretched during a contraction, the resulting steady-state force is higher than the isometric force produced at a comparable sarcomere length. This phenomenon, also referred to as residual force enhancement, cannot be readily explained by the force-sarcomere length relation. One of the most accepted mechanisms for the residual force enhancement is the development of sarcomere length non-uniformities after an active stretch. The aim of this study was to directly investigate the effect of non-uniformities on the force-producing capabilities of isolated myofibrils after they are actively stretched. We evaluated the effect of depleting a single A-band on sarcomere length non-uniformity and residual force enhancement. We observed that sarcomere length non-uniformity was effectively increased following A-band depletion. Furthermore, isometric forces decreased, while the percent residual force enhancement increased compared to intact myofibrils (5% vs. 20%). We conclude that sarcomere length non-uniformities are partially responsible for the enhanced force production after stretch.