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Impaired calcium handling in skeletal muscles of mitochondrial‐DNA‐mutator mice
Author(s) -
IVARSSON NIKLAS,
Hernández Andrés,
Bruton Joseph,
Westerblad Håkan
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1078.20
Subject(s) - skeletal muscle , atrophy , mitochondrial dna , medicine , mitochondrion , endocrinology , muscle atrophy , muscle weakness , endoplasmic reticulum , calcium , biology , stimulation , chemistry , microbiology and biotechnology , genetics , gene
Mitochondrial myopathies are diseases of the respiratory chain that lead to impaired muscle function. Mutations in mitochondrial DNA (mtDNA) have been proposed to cause weakness by inducing atrophy of skeletal muscle. Here, we examined muscle function in mice that express a proof‐reading‐deficient version of PolgA and display an increased number of mutations in the mtDNA and a premature aging phenotype, to examine skeletal muscle function. Force and free cytosolic [Ca2+] ([Ca2+]i) were measured in isolated fast‐twitch muscles of 11 month old mice. EDL muscles from mtDNA mutator mice were significantly smaller than controls (7.7 ± 0.3 vs. 11.2 ± 0.6 mg) and produced less force at 100 Hz stimulation (149.2 ± 12.5 vs. 291.1 ± 28.4 mN), indicating reduced force due to muscle atrophy. However, when force was expressed per cross sectional area, mtDNA muscles were weaker than controls (199.8 ± 25.2 vs. 286.7 ± 24.0 kPa). This was accompanied by reduced [Ca2+]i during tetanic contractions in mtDNA muscles (0.9 ± 0.1 vs. 2.1 ± 0.7 μM) and a ~50% reduction in expression of sarcoplasmic reticulum Ca2+‐ATPase‐1 (SERCA1) was observed. In conclusion, skeletal muscle weakness occurs due to both muscle atrophy and impaired Ca2+ handling in muscles from mtDNA mutator mice.