Increased expression of δCaMKII isoforms in skeletal muscle regeneration:: Implications in dystrophic muscle disease

The expression of 8 isoforms of calcium-calmodulin/dependent protein kinase 11 (CaMKII) has been reported in mammalian skeletal muscle; however, their functions in this tissue are largely unknown. This study was conducted to determine if delta CaMKII expression was altered during regeneration of skeletal muscle fibers in two distinct models. In the first model, necrosis and regeneration were induced in quadriceps of normal mice by intramuscular administration of 50% glycerol. Immunostaining and confocal microscopy revealed that delta CaMKII expression was clearly enhanced in fibers showing centralized nuclei. The second model was the mdx Mouse, which undergoes enhanced muscle necrosis and regeneration due to a mutation in the dystrophin gene. sern blot analysis of hind leg extracts from 4 to 6 week old mdx mice revealed that delta CaMKII content was decreased when compared to age-matched control mice. This loss in 6 kinase content was seen in myofibrillar and membrane fractions and was in contrast to unchanged delta CaMKII levels in cardiac and brain extracts from dystrophic mice. Confocal microscopy of mdx quadriceps and tibialis muscle showed that delta CaMKII expression was uniformly decreased in most fibers from dystrophic mice; however, enhanced kinase expression was observed in regenerating muscle fibers. These data Support a fundamental role for delta CaMKII in the regeneration process Of Muscle fibers in normal and mdx skeletal muscle and may have important implications in the reparative process following muscle death.