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Mini‐dystrophin restores L‐type calcium currents in skeletal muscle of transgenic mdx mice
Author(s) -
Friedrich O.,
Both M.,
Gillis J. M.,
Chamberlain J. S.,
Fink R. H. A.
Publication year - 2004
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2003.054213
Subject(s) - mdx mouse , dystrophin , duchenne muscular dystrophy , chemistry , calcium , biophysics , endocrinology , endoplasmic reticulum , medicine , skeletal muscle , genetically modified mouse , transgene , ryanodine receptor , dihydropyridine , muscular dystrophy , anatomy , biology , biochemistry , gene
L‐type calcium currents ( i Ca ) were recorded using the two‐microelectrode voltage‐clamp technique in single short toe muscle fibres of three different mouse strains: (i) C57/SV129 wild‐type mice (wt); (ii) mdx mice (an animal model for Duchenne muscular dystrophy; and (iii) transgenically engineered mini‐dystrophin (MinD)‐expressing mdx mice. The activation and inactivation properties of i Ca were examined in 2‐ to 18‐month‐old animals. Ca 2+ current densities at 0 mV in mdx fibres increased with age, but were always significantly smaller compared to age‐matched wild‐type fibres. Time‐to‐peak (TTP) of i Ca was prolonged in mdx fibres compared to wt fibres. MinD fibres always showed similar TTP and current amplitudes compared to age‐matched wt fibres. In all three genotypes, the voltage‐dependent inactivation and deactivation of i Ca were similar. Intracellular resting calcium concentration ([Ca 2+ ] i ) and the distribution of dihydropyridine binding sites were also not different in young animals of all three genotypes, whereas i Ca was markedly reduced in mdx fibres. We conclude, that dystrophin influences L‐type Ca 2+ channels via a direct or indirect linkage which may be disrupted in mdx mice and may be crucial for proper excitation–contraction coupling initiating Ca 2+ release from the sarcoplasmic reticulum. This linkage seems to be fully restored in the presence of mini‐dystrophin.