Cargando…
Restricting calcium currents is required for correct fiber type specification in skeletal muscle
Skeletal muscle excitation-contraction (EC) coupling is independent of calcium influx. In fact, alternative splicing of the voltage-gated calcium channel Ca(V)1.1 actively suppresses calcium currents in mature muscle. Whether this is necessary for normal development and function of muscle is not kno...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4909858/ https://www.ncbi.nlm.nih.gov/pubmed/26965373 http://dx.doi.org/10.1242/dev.129676 |
_version_ | 1782437898129244160 |
---|---|
author | Sultana, Nasreen Dienes, Beatrix Benedetti, Ariane Tuluc, Petronel Szentesi, Peter Sztretye, Monika Rainer, Johannes Hess, Michael W. Schwarzer, Christoph Obermair, Gerald J. Csernoch, Laszlo Flucher, Bernhard E. |
author_facet | Sultana, Nasreen Dienes, Beatrix Benedetti, Ariane Tuluc, Petronel Szentesi, Peter Sztretye, Monika Rainer, Johannes Hess, Michael W. Schwarzer, Christoph Obermair, Gerald J. Csernoch, Laszlo Flucher, Bernhard E. |
author_sort | Sultana, Nasreen |
collection | PubMed |
description | Skeletal muscle excitation-contraction (EC) coupling is independent of calcium influx. In fact, alternative splicing of the voltage-gated calcium channel Ca(V)1.1 actively suppresses calcium currents in mature muscle. Whether this is necessary for normal development and function of muscle is not known. However, splicing defects that cause aberrant expression of the calcium-conducting developmental Ca(V)1.1e splice variant correlate with muscle weakness in myotonic dystrophy. Here, we deleted Ca(V)1.1 (Cacna1s) exon 29 in mice. These mice displayed normal overall motor performance, although grip force and voluntary running were reduced. Continued expression of the developmental Ca(V)1.1e splice variant in adult mice caused increased calcium influx during EC coupling, altered calcium homeostasis, and spontaneous calcium sparklets in isolated muscle fibers. Contractile force was reduced and endurance enhanced. Key regulators of fiber type specification were dysregulated and the fiber type composition was shifted toward slower fibers. However, oxidative enzyme activity and mitochondrial content declined. These findings indicate that limiting calcium influx during skeletal muscle EC coupling is important for the secondary function of the calcium signal in the activity-dependent regulation of fiber type composition and to prevent muscle disease. |
format | Online Article Text |
id | pubmed-4909858 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-49098582016-07-14 Restricting calcium currents is required for correct fiber type specification in skeletal muscle Sultana, Nasreen Dienes, Beatrix Benedetti, Ariane Tuluc, Petronel Szentesi, Peter Sztretye, Monika Rainer, Johannes Hess, Michael W. Schwarzer, Christoph Obermair, Gerald J. Csernoch, Laszlo Flucher, Bernhard E. Development Research Article Skeletal muscle excitation-contraction (EC) coupling is independent of calcium influx. In fact, alternative splicing of the voltage-gated calcium channel Ca(V)1.1 actively suppresses calcium currents in mature muscle. Whether this is necessary for normal development and function of muscle is not known. However, splicing defects that cause aberrant expression of the calcium-conducting developmental Ca(V)1.1e splice variant correlate with muscle weakness in myotonic dystrophy. Here, we deleted Ca(V)1.1 (Cacna1s) exon 29 in mice. These mice displayed normal overall motor performance, although grip force and voluntary running were reduced. Continued expression of the developmental Ca(V)1.1e splice variant in adult mice caused increased calcium influx during EC coupling, altered calcium homeostasis, and spontaneous calcium sparklets in isolated muscle fibers. Contractile force was reduced and endurance enhanced. Key regulators of fiber type specification were dysregulated and the fiber type composition was shifted toward slower fibers. However, oxidative enzyme activity and mitochondrial content declined. These findings indicate that limiting calcium influx during skeletal muscle EC coupling is important for the secondary function of the calcium signal in the activity-dependent regulation of fiber type composition and to prevent muscle disease. The Company of Biologists Ltd 2016-05-01 /pmc/articles/PMC4909858/ /pubmed/26965373 http://dx.doi.org/10.1242/dev.129676 Text en © 2016. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Sultana, Nasreen Dienes, Beatrix Benedetti, Ariane Tuluc, Petronel Szentesi, Peter Sztretye, Monika Rainer, Johannes Hess, Michael W. Schwarzer, Christoph Obermair, Gerald J. Csernoch, Laszlo Flucher, Bernhard E. Restricting calcium currents is required for correct fiber type specification in skeletal muscle |
title | Restricting calcium currents is required for correct fiber type specification in skeletal muscle |
title_full | Restricting calcium currents is required for correct fiber type specification in skeletal muscle |
title_fullStr | Restricting calcium currents is required for correct fiber type specification in skeletal muscle |
title_full_unstemmed | Restricting calcium currents is required for correct fiber type specification in skeletal muscle |
title_short | Restricting calcium currents is required for correct fiber type specification in skeletal muscle |
title_sort | restricting calcium currents is required for correct fiber type specification in skeletal muscle |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4909858/ https://www.ncbi.nlm.nih.gov/pubmed/26965373 http://dx.doi.org/10.1242/dev.129676 |
work_keys_str_mv | AT sultananasreen restrictingcalciumcurrentsisrequiredforcorrectfibertypespecificationinskeletalmuscle AT dienesbeatrix restrictingcalciumcurrentsisrequiredforcorrectfibertypespecificationinskeletalmuscle AT benedettiariane restrictingcalciumcurrentsisrequiredforcorrectfibertypespecificationinskeletalmuscle AT tulucpetronel restrictingcalciumcurrentsisrequiredforcorrectfibertypespecificationinskeletalmuscle AT szentesipeter restrictingcalciumcurrentsisrequiredforcorrectfibertypespecificationinskeletalmuscle AT sztretyemonika restrictingcalciumcurrentsisrequiredforcorrectfibertypespecificationinskeletalmuscle AT rainerjohannes restrictingcalciumcurrentsisrequiredforcorrectfibertypespecificationinskeletalmuscle AT hessmichaelw restrictingcalciumcurrentsisrequiredforcorrectfibertypespecificationinskeletalmuscle AT schwarzerchristoph restrictingcalciumcurrentsisrequiredforcorrectfibertypespecificationinskeletalmuscle AT obermairgeraldj restrictingcalciumcurrentsisrequiredforcorrectfibertypespecificationinskeletalmuscle AT csernochlaszlo restrictingcalciumcurrentsisrequiredforcorrectfibertypespecificationinskeletalmuscle AT flucherbernharde restrictingcalciumcurrentsisrequiredforcorrectfibertypespecificationinskeletalmuscle |