Ca2+‐ and Sr2+‐activated contractile characteristics of permeabilized muscle fibers from dystrophic dogs

Abstract

The Golden Retriever muscular dystrophy (GRMD) dog has a mutation in the dystrophin gene, suffers muscle wasting and weakness, and dies prematurely from cardiac or pulmonary failure. It is a relevant model for understanding the underlying mechanisms and investigating potential therapeutic approaches for Duchenne muscular dystrophy (DMD). Unfortunately, few GRMD colonies exist worldwide and there is a lack of information regarding aspects of muscle fiber function between dystrophic and healthy dogs. Our aim was to identify Ca2+‐ and Sr2+‐activated contractile characteristics of single permeabilized fibers from the biceps femoris muscles of 2‐year old GRMD dogs. Single fibers were attached to a force transducer, activated in Ca2+‐ and Sr2+‐buffered solutions to generate force‐pCa(pSr) relations, and then analyzed for myosin heavy chain and troponin‐C isoform composition. Specific force was ~25% lower in dystrophic dogs compared with litter mate controls (215 ± 18 kN/m2, n = 15 vs 160 ± 9 kN/m2, n = 15), but fiber sensitivity to Ca2+ was unchanged. A high proportion (~65%) of fibers from dystrophic dogs were ‘hybrid’ fibers as evident from their biphasic force‐pSr relations and combination of slow and fast troponin‐C isoforms. These functional assessments provide important information about the progression of muscular dystrophy in the GRMD model and its relevance to DMD.Supported by the Muscular Dystrophy Association (USA)