John A. Faulkner

Sarcospan-Deficient Mice Maintain Normal Muscle Function

ABSTRACT Sarcospan is an integral membrane component of the dystrophin-glycoprotein complex (DGC) found at the sarcolemma of striated and smooth muscle. The DGC plays important roles in muscle function and viability as evidenced by defects in components of the DGC, which cause muscular dystrophy. Sarcospan is unique among the components of the complex in that it contains four transmembrane domains with intracellular N- and C-terminal domains and is a member of the tetraspan superfamily of proteins. Sarcospan is tightly linked to the sarcoglycans, and together these proteins form a subcomplex within the DGC. Stable expression of sarcospan at the sarcolemma is dependent upon expression of the sarcoglycans. Here we describe the generation and analysis of mice carrying a null mutation in the Sspngene. Surprisingly, the Sspn-deficient muscle maintains expression of other components of the DGC at the sarcolemma, and no gross histological abnormalities of muscle from the mice are observed. The Sspn-deficient muscle maintains sarcolemmal integrity as determined by serum creatine kinase and Evans blue uptake assays, and the Sspn-deficient muscle maintains normal force and power generation capabilities. These data suggest either that sarcospan is not required for normal DGC function or that theSspn-deficient muscle is compensating for the absence of sarcospan, perhaps by utilizing another protein to carry out its function.

Motor unit function in skeletal muscle autografts of rats

Standard and nerve-intact grafts of the extensor digitorum longus (EDL) muscles of rats do not fully recover control values for maximum tetanic tension (Po). We compared the physiologic properties of motor units from standard and nerve-intact EDL grafts of rats with those of control EDL muscles. Standard grafts were completely removed and replaced in their original site. For nerve-intact grafts all physical connections were severed except for the nerve. Isometric contractile properties of whole muscles and single motor units were measured in situ 75 and 50 days after surgery for standard and nerve-intact grafts, respectively. Motor units from both types of grafts showed a mean and distribution for time-to-peak twitch tension (TPT) not different from control motor units. The absolute Po of nerve-intact grafts showed a greater recovery than the standard grafts, but was still significantly lower than the control value. The average decrease in the Po of motor units from nerve-intact grafts of 16% was not different from the decrease in the Po of the total EDL graft which suggests no loss of motor units in nerve-intact grafts. In standard grafts, the 57% decrease in Po for the whole muscle was attributable to a 20% decrease in the average tension development per motor unit and a 45% decrease in the number of motor units. These differences suggest a more complete reinnervation of the nerve-intact grafts than standard grafts.

Characterization of skeletal muscle effects associated with daptomycin in rats

Daptomycin is a lipopeptide antibiotic with strong bactericidal effects against Gram‐positive bacteria and minor side effects on skeletal muscles. The type and magnitude of the early effect of daptomycin on skeletal muscles of rats was quantified by histopathology, examination of contractile properties, Evans Blue Dye uptake, and effect on the patch repair process. A single dose of daptomycin of up to 200 mg/kg had no effect on muscle fibers. A dose of 150 mg/kg of daptomycin, twice per day for 3 days, produced a small number of myofibers (≤0.22%) with loss of plasma membrane integrity and/or infiltration by neutrophils and/or macrophages. Multiple doses of daptomycin are required for a quantifiable effect on skeletal muscles of rats. Some fibers were Evans Blue Dye–positive but were not yet infiltrated by neutrophils. This suggests that the sarcolemma may be the primary target for the observed effects. Muscle Nerve, 2010