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Increased calcium entry into dystrophin‐deficient muscle fibres of MDX and ADR‐MDX mice is reduced by ion channel blockers
Author(s) -
Tutdibi O.,
Brinkmeier H.,
Rüdel R.,
Föhr K. J.
Publication year - 1999
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 - 10.1111/j.1469-7793.1999.859ab.x
Subject(s) - mdx mouse , chemistry , biophysics , duchenne muscular dystrophy , calcium , dystrophin , amiloride , medicine , endocrinology , sodium , biology , organic chemistry
1 Single fibres were enzymatically isolated from interosseus muscles of dystrophic MDX mice, myotonic‐dystrophic double mutant ADR‐MDX mice and C57BL/10 controls. The fibres were kept in cell culture for up to 2 weeks for the study of Ca 2+ homeostasis and sarcolemmal Ca 2+ permeability. 2 Resting levels of intracellular free Ca 2+ , determined with the fluorescent Ca 2+ indicator fura‐2, were slightly higher in MDX (63 ± 20 n m ; means ± s.d. ; n = 454 analysed fibres) and ADR‐MDX (65 ± 12 n m ; n = 87 ) fibres than in controls (51 ± 20 n m ; n = 265 ). 3 The amplitudes of electrically induced Ca 2+ transients did not differ between MDX fibres and controls. Decay time constants of Ca 2+ transients ranged between 10 and 55 ms in both genotypes. In 50% of MDX fibres ( n = 68 ), but in only 20% of controls ( n = 54 ), the decay time constants were > 35 ms. 4 Bath application of Mn 2+ resulted in a progressive quench of fura‐2 fluorescence emitted from the fibres. The quench rate was about 2 times higher in MDX fibres (3.98 ± 1.9% min −1 ; n = 275 ) than in controls (2.03 ± 1.4% min −1 ; n = 204 ). The quench rate in ADR‐MDX fibres (2.49 ± 1.4% min −1 ; n = 87 ) was closer to that of controls. 5 The Mn 2+ influx into MDX fibres was reduced to 10% by Gd 3+ , to 19% by La 3+ and to 47% by Ni 2+ (all at 50 μ m ). Bath application of 50 μ m amiloride inhibited the Mn 2+ influx to 37%. 6 We conclude that in isolated, resting MDX muscle fibres the membrane permeability for divalent cations is increased. The presumed additional influx of Ca 2+ occurs through ion channels, but is well compensated for by effective cellular Ca 2+ transport systems. The milder dystrophic phenotype of ADR‐MDX mice is correlated with a smaller increase of their sarcolemmal Ca 2+ permeability.