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Comparison of the myoplasmic calcium transient elicited by an action potential in intact fibres of mdx and normal mice
Author(s) -
Hollingworth Stephen,
Zeiger Ulrike,
Baylor Stephen M.
Publication year - 2008
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.2008.160507
Subject(s) - calcium , biophysics , chemistry , anatomy , endoplasmic reticulum , medicine , biology , biochemistry , organic chemistry
The myoplasmic free [Ca 2+ ] transient elicited by an action potential (Δ[Ca 2+ ]) was compared in fast‐twitch fibres of mdx (dystrophin null) and normal mice. Methods were used that maximized the likelihood that any detected differences apply in vivo . Small bundles of fibres were manually dissected from extensor digitorum longus muscles of 7‐ to 14‐week‐old mice. One fibre within a bundle was microinjected with furaptra, a low‐affinity rapidly responding fluorescent calcium indicator. A fibre was accepted for study if it gave a stable, all‐or‐nothing fluorescence response to an external shock. In 18 normal fibres, the peak amplitude and the full‐duration at half‐maximum (FDHM) of Δ[Ca 2+ ] were 18.4 ± 0.5 μ m and 4.9 ± 0.2 ms, respectively (mean ± s.e.m. ; 16°C). In 13 mdx fibres, the corresponding values were 14.5 ± 0.6 μ m and 4.7 ± 0.2 ms. The difference in amplitude is statistically highly significant ( P = 0.0001; two‐tailed t test), whereas the difference in FDHM is not ( P = 0.3). A multi‐compartment computer model was used to estimate the amplitude and time course of the sarcoplasmic reticulum (SR) calcium release flux underlying Δ[Ca 2+ ]. Estimates were made based on several differing assumptions: (i) that the resting myoplasmic free Ca 2+ concentration ([Ca 2+ ] R ) and the total concentration of parvalbumin ([Parv T ]) are the same in mdx and normal fibres, (ii) that [Ca 2+ ] R is larger in mdx fibres, (iii) that [Parv T ] is smaller in mdx fibres, and (iv) that [Ca 2+ ] R is larger and [Parv T ] is smaller in mdx fibres. According to the simulations, the 21% smaller amplitude of Δ[Ca 2+ ] in mdx fibres in combination with the unchanged FDHM of Δ[Ca 2+ ] is consistent with mdx fibres having a ∼25% smaller flux amplitude, a 6–23% larger FDHM of the flux, and a 9–20% smaller total amount of released Ca 2+ than normal fibres. The changes in flux are probably due to a change in the gating of the SR Ca 2+ ‐release channels and/or in their single channel flux. The link between these changes and the absence of dystrophin remains to be elucidated.