1. Titin is required for lateral stability of myosin filament lattice. The spacing of nearest-neighbor myosin filaments in electromicrographs of cross sections through the A band was measured in irradiated muscle fibers. The irradiation dose was selected to degrade the titin molecules but leave the smaller molecules intact. The average filament spacing was the same in irradiated and control fibers, but the standard deviation of the control fiber spacing distribution was smaller. This result is evidence that the presence of intact titin promotes lateral order in the array of myosin filaments. 2. Crosslinking of the rod portion of the myosin thick filaments interferes with the crosslinking between the myosin and actin. SDS polyacrylamide gel electrophoresis was carried out to examine the fraction of myosin heads that are crosslinked to actin with EDC. EDC treatment gave 10 times more crosslinking when it followed chymotryptic digestion as opposed to preceding the digestion. The results suggest that only a small fraction of the myosin heads are crosslinked to actin by EDC. This differs from crosslinking assays based on mechanical experiments; these show that essentially every myosin molecule is crosslinked to actin under these conditions (Iwamoto and Podolsky, 1992). Studies to resolve this discrepancy are under way. 3. Properties of mutant myosin in muscle fibers from patients with familial hypertrophic cardiomyopathy (FHC). The contractile force of calcium activated, skinned soleus muscle fibers was measured in control fibers and in mutants 403, 741, and 908. The force was normal in mutants 741 and 908, but half normal in 403. It is concluded that subnormal force is not an essential features of FHC.

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National Institute of Arthritis and Musculoskeletal and Skin Diseases
United States
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