Variable cytoplasmic actin expression impacts the sensitivity of different dystrophin-deficient mdx skeletal muscles to eccentric contraction

Angus Lindsay, William M. Southern, Preston M. McCourt, Alexie A. Larson, James S Hodges, Dawn A Lowe, James M Ervasti

Research output: Contribution to journalArticle

Abstract

Eccentric contractions (ECCs) induce force loss in several skeletal muscles of dystrophin-deficient mice (mdx), with the exception of the soleus (Sol). The eccentric force : isometric force (ECC : ISO), expression level of utrophin, fiber type distribution, and sarcoendoplasmic reticulum calcium ATPase expression are factors that differ between muscles and may contribute to the sensitivity of mdx skeletal muscle to ECC. Here, we confirm that the Sol of mdx mice loses only 13% force compared to 87% in the extensor digitorum longus (EDL) following 10 ECC of isolated muscles. The Sol has a greater proportion of fibers expressing Type I myosin heavy chain (MHC) and expresses 2.3-fold more utrophin compared to the EDL. To examine the effect of ECC : ISO, we show that the mdx Sol is insensitive to ECC at ECC : ISO up to 230 ± 15%. We show that the peroneus longus (PL) muscle presents with similar ECC : ISO compared to the EDL, intermediate force loss (68%) following 10 ECC, and intermediate fiber type distribution and utrophin expression relative to EDL and Sol. The combined absence of utrophin and dystrophin in mdx/utrophin−/− mice rendered the Sol only partially susceptible to ECC and exacerbated force loss in the EDL and PL. Most interestingly, the expression levels of cytoplasmic β- and γ-actins correlate inversely with a given muscle's sensitivity to ECC; EDL < PL < Sol. Our data indicate that fiber type, utrophin, and cytoplasmic actin expression all contribute to the differential sensitivities of mdxEDL, PL, and Sol muscles to ECC.

Original languageEnglish (US)
Pages (from-to)2562-2576
Number of pages15
JournalFEBS Journal
Volume286
Issue number13
DOIs
StatePublished - Jul 1 2019

Fingerprint

Utrophin
Dystrophin
Muscle
Actins
Skeletal Muscle
Inbred mdx Mouse
Muscles
Fibers
Reticulum
Calcium-Transporting ATPases
Myosin Heavy Chains
Muscle Contraction

Keywords

  • Duchenne muscular dystrophy
  • cytoplasmic actin
  • eccentric contraction
  • myosin heavy chain
  • utrophin

PubMed: MeSH publication types

  • Journal Article

Cite this

Variable cytoplasmic actin expression impacts the sensitivity of different dystrophin-deficient mdx skeletal muscles to eccentric contraction. / Lindsay, Angus; Southern, William M.; McCourt, Preston M.; Larson, Alexie A.; Hodges, James S; Lowe, Dawn A; Ervasti, James M.

In: FEBS Journal, Vol. 286, No. 13, 01.07.2019, p. 2562-2576.

Research output: Contribution to journalArticle

@article{c5c43c2df7574aabb215a4f748b80f1a,
title = "Variable cytoplasmic actin expression impacts the sensitivity of different dystrophin-deficient mdx skeletal muscles to eccentric contraction",
abstract = "Eccentric contractions (ECCs) induce force loss in several skeletal muscles of dystrophin-deficient mice (mdx), with the exception of the soleus (Sol). The eccentric force : isometric force (ECC : ISO), expression level of utrophin, fiber type distribution, and sarcoendoplasmic reticulum calcium ATPase expression are factors that differ between muscles and may contribute to the sensitivity of mdx skeletal muscle to ECC. Here, we confirm that the Sol of mdx mice loses only 13{\%} force compared to 87{\%} in the extensor digitorum longus (EDL) following 10 ECC of isolated muscles. The Sol has a greater proportion of fibers expressing Type I myosin heavy chain (MHC) and expresses 2.3-fold more utrophin compared to the EDL. To examine the effect of ECC : ISO, we show that the mdx Sol is insensitive to ECC at ECC : ISO up to 230 ± 15{\%}. We show that the peroneus longus (PL) muscle presents with similar ECC : ISO compared to the EDL, intermediate force loss (68{\%}) following 10 ECC, and intermediate fiber type distribution and utrophin expression relative to EDL and Sol. The combined absence of utrophin and dystrophin in mdx/utrophin−/− mice rendered the Sol only partially susceptible to ECC and exacerbated force loss in the EDL and PL. Most interestingly, the expression levels of cytoplasmic β- and γ-actins correlate inversely with a given muscle's sensitivity to ECC; EDL < PL < Sol. Our data indicate that fiber type, utrophin, and cytoplasmic actin expression all contribute to the differential sensitivities of mdxEDL, PL, and Sol muscles to ECC.",
keywords = "Duchenne muscular dystrophy, cytoplasmic actin, eccentric contraction, myosin heavy chain, utrophin",
author = "Angus Lindsay and Southern, {William M.} and McCourt, {Preston M.} and Larson, {Alexie A.} and Hodges, {James S} and Lowe, {Dawn A} and Ervasti, {James M}",
year = "2019",
month = "7",
day = "1",
doi = "10.1111/febs.14831",
language = "English (US)",
volume = "286",
pages = "2562--2576",
journal = "FEBS Journal",
issn = "1742-464X",
publisher = "Wiley-Blackwell",
number = "13",

}

TY - JOUR

T1 - Variable cytoplasmic actin expression impacts the sensitivity of different dystrophin-deficient mdx skeletal muscles to eccentric contraction

AU - Lindsay, Angus

AU - Southern, William M.

AU - McCourt, Preston M.

AU - Larson, Alexie A.

AU - Hodges, James S

AU - Lowe, Dawn A

AU - Ervasti, James M

PY - 2019/7/1

Y1 - 2019/7/1

N2 - Eccentric contractions (ECCs) induce force loss in several skeletal muscles of dystrophin-deficient mice (mdx), with the exception of the soleus (Sol). The eccentric force : isometric force (ECC : ISO), expression level of utrophin, fiber type distribution, and sarcoendoplasmic reticulum calcium ATPase expression are factors that differ between muscles and may contribute to the sensitivity of mdx skeletal muscle to ECC. Here, we confirm that the Sol of mdx mice loses only 13% force compared to 87% in the extensor digitorum longus (EDL) following 10 ECC of isolated muscles. The Sol has a greater proportion of fibers expressing Type I myosin heavy chain (MHC) and expresses 2.3-fold more utrophin compared to the EDL. To examine the effect of ECC : ISO, we show that the mdx Sol is insensitive to ECC at ECC : ISO up to 230 ± 15%. We show that the peroneus longus (PL) muscle presents with similar ECC : ISO compared to the EDL, intermediate force loss (68%) following 10 ECC, and intermediate fiber type distribution and utrophin expression relative to EDL and Sol. The combined absence of utrophin and dystrophin in mdx/utrophin−/− mice rendered the Sol only partially susceptible to ECC and exacerbated force loss in the EDL and PL. Most interestingly, the expression levels of cytoplasmic β- and γ-actins correlate inversely with a given muscle's sensitivity to ECC; EDL < PL < Sol. Our data indicate that fiber type, utrophin, and cytoplasmic actin expression all contribute to the differential sensitivities of mdxEDL, PL, and Sol muscles to ECC.

AB - Eccentric contractions (ECCs) induce force loss in several skeletal muscles of dystrophin-deficient mice (mdx), with the exception of the soleus (Sol). The eccentric force : isometric force (ECC : ISO), expression level of utrophin, fiber type distribution, and sarcoendoplasmic reticulum calcium ATPase expression are factors that differ between muscles and may contribute to the sensitivity of mdx skeletal muscle to ECC. Here, we confirm that the Sol of mdx mice loses only 13% force compared to 87% in the extensor digitorum longus (EDL) following 10 ECC of isolated muscles. The Sol has a greater proportion of fibers expressing Type I myosin heavy chain (MHC) and expresses 2.3-fold more utrophin compared to the EDL. To examine the effect of ECC : ISO, we show that the mdx Sol is insensitive to ECC at ECC : ISO up to 230 ± 15%. We show that the peroneus longus (PL) muscle presents with similar ECC : ISO compared to the EDL, intermediate force loss (68%) following 10 ECC, and intermediate fiber type distribution and utrophin expression relative to EDL and Sol. The combined absence of utrophin and dystrophin in mdx/utrophin−/− mice rendered the Sol only partially susceptible to ECC and exacerbated force loss in the EDL and PL. Most interestingly, the expression levels of cytoplasmic β- and γ-actins correlate inversely with a given muscle's sensitivity to ECC; EDL < PL < Sol. Our data indicate that fiber type, utrophin, and cytoplasmic actin expression all contribute to the differential sensitivities of mdxEDL, PL, and Sol muscles to ECC.

KW - Duchenne muscular dystrophy

KW - cytoplasmic actin

KW - eccentric contraction

KW - myosin heavy chain

KW - utrophin

UR - http://www.scopus.com/inward/record.url?scp=85064499715&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064499715&partnerID=8YFLogxK

U2 - 10.1111/febs.14831

DO - 10.1111/febs.14831

M3 - Article

C2 - 30942954

AN - SCOPUS:85064499715

VL - 286

SP - 2562

EP - 2576

JO - FEBS Journal

JF - FEBS Journal

SN - 1742-464X

IS - 13

ER -