L-type Ca2+ channel function is linked to dystrophin expression in mammalian muscle.
Friedrich O, von Wegner F, Chamberlain JS, Fink R, Rohrbach P (2008)
Publication Language: English
Publication Status: Published
Publication Type: Journal article, Original article
Publication year: 2008
Journal
Publisher: Public Library of Science
Book Volume: 3
Pages Range: e1762
Journal Issue: 3
URI: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0001762
DOI: 10.1371/journal.pone.0001762
Open Access Link: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0001762
Abstract
BACKGROUND\nIn dystrophic mdx skeletal muscle, aberrant Ca2+ homeostasis and fibre degeneration are found. The absence of dystrophin in models of Duchenne muscular dystrophy (DMD) has been connected to altered ion channel properties e.g. impaired L-type Ca2+ currents. In regenerating mdx muscle, 'revertant' fibres restore dystrophin expression. Their functionality involving DHPR-Ca2+-channels is elusive.\nMETHODS AND RESULTS\nWe developed a novel 'in-situ' confocal immuno-fluorescence and imaging technique that allows, for the first time, quantitative subcellular dystrophin-DHPR colocalization in individual, non-fixed, muscle fibres. Tubular DHPR signals alternated with second harmonic generation signals originating from myosin. Dystrophin-DHPR colocalization was substantial in wt fibres, but diminished in most mdx fibres. Mini-dystrophin (MinD) expressing fibres successfully restored colocalization. Interestingly, in some aged mdx fibres, colocalization was similar to wt fibres. Most mdx fibres showed very weak membrane dystrophin staining and were classified 'mdx-like'. Some mdx fibres, however, had strong 'wt-like' dystrophin signals and were identified as 'revertants'. Split mdx fibres were mostly 'mdx-like' and are not generally 'revertants'. Correlations between membrane dystrophin and DHPR colocalization suggest a restored putative link in 'revertants'. Using the two-micro-electrode-voltage clamp technique, Ca2+-current amplitudes (i(max)) showed very similar behaviours: reduced amplitudes in most aged mdx fibres (as seen exclusively in young mdx mice) and a few mdx fibres, most likely 'revertants', with amplitudes similar to wt or MinD fibres. Ca2+ current activation curves were similar in 'wt-like' and 'mdx-like' aged mdx fibres and are not the cause for the differences in current amplitudes. i(max) amplitudes were fully restored in MinD fibres.\nCONCLUSIONS\nWe present evidence for a direct/indirect DHPR-dystrophin interaction present in wt, MinD and 'revertant' mdx fibres but absent in remaining mdx fibres. Our imaging technique reliably detects single isolated 'revertant' fibres that could be used for subsequent physiological experiments to study mechanisms and therapy concepts in DMD.
Authors with CRIS profile
Involved external institutions
University of Washington
United States (USA) (US)
Ruprecht-Karls-Universität Heidelberg
Germany (DE)
McGill University
Canada (CA)
Goethe-Universität Frankfurt am Main
Germany (DE)
United States (USA) (US)
Ruprecht-Karls-Universität Heidelberg
Germany (DE)
McGill University
Canada (CA)
Goethe-Universität Frankfurt am Main
Germany (DE)
How to cite
APA:
Friedrich, O., von Wegner, F., Chamberlain, J.S., Fink, R., & Rohrbach, P. (2008). L-type Ca2+ channel function is linked to dystrophin expression in mammalian muscle. PLoS ONE, 3(3), e1762. https://doi.org/10.1371/journal.pone.0001762
MLA:
Friedrich, Oliver, et al. "L-type Ca2+ channel function is linked to dystrophin expression in mammalian muscle." PLoS ONE 3.3 (2008): e1762.
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