Alteration of excitation-contraction coupling mechanism in extensor digitorum longus muscle fibres of dystrophic mdx mouse and potential efficacy of taurine
A. De Luca et al., Alteration of excitation-contraction coupling mechanism in extensor digitorum longus muscle fibres of dystrophic mdx mouse and potential efficacy of taurine, BR J PHARM, 132(5), 2001, pp. 1047-1054
1 No clear data is available about functional alterations in the calcium-de
pendent excitation-contraction (e-c) coupling mechanism of dystrophin-defic
ient muscle of mdx mice.
2 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 m
dx mouse of two different ages: 8-12 weeks, during the active regeneration
of hind limb muscles, and 6-8 months, when regeneration is complete.
3 The EDL muscle fibres of 8-12-week-old wildtype animals had a more negati
ve rheobase voltage (potential of equilibrium for contraction- and relaxati
on-related calcium movements) with respect to control mice of 6-8 months. H
owever, at both ages, the EDL muscle fibres of mdx mice contracted at more
negative potentials with respect to age-matched controls and had markedly s
lower time constants to reach the rheobase.
4 The in vitro application of 60 mM taurine, whose normally high intracellu
lar muscle levels play a role in e-c coupling, was without effect on 6-8-mo
nth-old wildtype EDL muscle, while it significantly ameliorated the MT of m
dx mouse.
5 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 a
mino acid levels in hind limb muscles, brain and heart, suggesting a tissue
difficulty in retaining appropriate levels of the amino acid.
6 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 increas
e in intracellular calcium, and can be ameliorated by taurine, suggesting a
potential therapeutic role of the amino acid.