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Alteration of excitation‐contraction coupling mechanism in extensor digitorum longus muscle fibres of dystrophic mdx mouse and potential efficacy of taurine
Author(s) -
De Luca Annamaria,
Pierno Sabata,
Liantonio Antonella,
Cetrone Michela,
Camerino Claudia,
Simonetti Simonetta,
Papadia Francesco,
Camerino Diana Conte
Publication year - 2001
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703907
Subject(s) - taurine , mdx mouse , rheobase , extensor digitorum longus muscle , medicine , endocrinology , chemistry , contraction (grammar) , sarcolemma , hindlimb , muscle contraction , anatomy , skeletal muscle , biophysics , electrophysiology , biology , amino acid , dystrophin , biochemistry
No clear data is available about functional alterations in the calcium‐dependent excitation‐contraction (e‐c) coupling mechanism of dystrophin‐deficient muscle of mdx mice. By means of the intracellular microelectrode ‘point’ voltage clamp method, we measured the voltage threshold for contraction (mechanical threshold; MT) in intact extensor digitorum longus (EDL) muscle fibres of dystrophic mdx mouse of two different ages: 8–12 weeks, during the active regeneration of hind limb muscles, and 6–8 months, when regeneration is complete. The EDL muscle fibres of 8–12‐week‐old wildtype animals had a more negative rheobase voltage (potential of equilibrium for contraction‐ and relaxation‐related calcium movements) with respect to control mice of 6–8 months. However, at both ages, the EDL muscle fibres of mdx mice contracted at more negative potentials with respect to age‐matched controls and had markedly slower time constants to reach the rheobase. The in vitro application of 60 m M taurine, whose normally high intracellular muscle levels play a role in e‐c coupling, was without effect on 6–8‐month‐old wildtype EDL muscle, while it significantly ameliorated the MT of mdx mouse. HPLC determination of taurine content at 6–8 months showed a significant 140% rise of plasma taurine levels and a clear trend toward a decrease in amino acid levels in hind limb muscles, brain and heart, suggesting a tissue difficulty in retaining appropriate levels of the amino acid. The data is consistent with a permanent alteration of e‐c coupling in mdx EDL muscle fibres. The alteration could be related to the proposed increase in intracellular calcium, and can be ameliorated by taurine, suggesting a potential therapeutic role of the amino acid.British Journal of Pharmacology (2001) 132 , 1047–1054; doi: 10.1038/sj.bjp.0703907