Lower active force generation and improved fatigue resistance in skeletal muscle from desmin defficient mice

The mechanical effects of the intermediate. lament protein desmin was examined in desmin deficient mice (Des-/-) and their wild type control ( Des +/+). Active force generation was determined in intact soleus muscles and in skinned single fibres from soleus and psoas. A decreased force generation of skinned muscle fibres from Des-/- mice and a tendency towards decreased active force in intact soleus muscle were detected. Concentrations of the contractile protein actin and myosin were not altered in Des-/- muscles. Ca2+-sensitivity of skinned single fibres in Des-/- muscles was unchanged compared to Des+/+. Using a protocol with repeated short tetani an increased fatigue resistance was found in the intact soleus muscles from Des-/- mice. In conclusion, desmin intermediate. laments are required for optimal generation or transmission of active force in skeletal muscle. Although other studies have shown that the desmin intermediate. laments appear to influence Ca2+-handling, the Ca2+-sensitivity of the contractile. laments is not altered in skeletal muscle of Des-/- mice. Previous studies have reported a switch towards slower myosin isoforms in slow skeletal muscle of Des-/- mice. The increased fatigue resistance show that this change is reflected in the physiological function of the muscle.