Effects of stretch‐activated channel blockers on [Ca2+]i and muscle damage in the mdx mouse

Yeung, Ella W.; Whitehead, Nicholas P.; Suchyna, Thomas M.; Gottlieb, Philip A.; Sachs, Frederick; Allen, David G.

doi:10.1113/jphysiol.2004.075275

Cited by 244 publications

(306 citation statements)

References 56 publications

(92 reference statements)

Supporting

Mentioning

288

Contrasting

Unclassified

Order By: Relevance

“…Exposure of muscles of mdx mice to either calcium-free buffer or buffer supplemented with the antioxidant N-acetylcysteine (NAC) decreased contraction-induced force deficits to 50% of those in control buffer (Fig. 3A and Table S2), confirming earlier reports regarding mdx mice (28)(29)(30)(31). In contrast, muscles of inducible DG KO mice were unresponsive to the conditions of calcium-free buffer and antioxidant supplementation (Fig.…”

Section: Evidence Of Titin Disruption Rather Than Increased Sarcolemmsupporting

confidence: 88%

“…In dystrophic muscles, damage mediated by extracellular calcium or reactive oxygen species is a consequence of increased membrane permeability (28)(29)(30). Exposure of muscles of mdx mice to either calcium-free buffer or buffer supplemented with the antioxidant N-acetylcysteine (NAC) decreased contraction-induced force deficits to 50% of those in control buffer (Fig.…”

Section: Evidence Of Titin Disruption Rather Than Increased Sarcolemmmentioning

confidence: 99%

See 1 more Smart Citation

Role of dystroglycan in limiting contraction-induced injury to the sarcomeric cytoskeleton of mature skeletal muscle

Rader

Turk

Willer

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Dystroglycan (DG) is a highly expressed extracellular matrix receptor that is linked to the cytoskeleton in skeletal muscle. DG is critical for the function of skeletal muscle, and muscle with primary defects in the expression and/or function of DG throughout development has many pathological features and a severe muscular dystrophy phenotype. In addition, reduction in DG at the sarcolemma is a common feature in muscle biopsies from patients with various types of muscular dystrophy. However, the consequence of disrupting DG in mature muscle is not known. Here, we investigated muscles of transgenic mice several months after genetic knockdown of DG at maturity. In our study, an increase in susceptibility to contractioninduced injury was the first pathological feature observed after the levels of DG at the sarcolemma were reduced. The contractioninduced injury was not accompanied by increased necrosis, excitation-contraction uncoupling, or fragility of the sarcolemma. Rather, disruption of the sarcomeric cytoskeleton was evident as reduced passive tension and decreased titin immunostaining. These results reveal a role for DG in maintaining the stability of the sarcomeric cytoskeleton during contraction and provide mechanistic insight into the cause of the reduction in strength that occurs in muscular dystrophy after lengthening contractions. muscular dystrophy | eccentric contraction | titin | skeletal muscle | dystroglycan

show abstract

Section: Evidence Of Titin Disruption Rather Than Increased Sarcolemmsupporting

confidence: 88%

Section: Evidence Of Titin Disruption Rather Than Increased Sarcolemmmentioning

confidence: 99%

Role of dystroglycan in limiting contraction-induced injury to the sarcomeric cytoskeleton of mature skeletal muscle

Rader

Turk

Willer

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…There is evidence for increased active Ca 2+ transport across the sarcolemmal membrane resulting from activation of stretch sensitive Ca 2+ channels (8) and increased L-type Ca 2+ channel activity (9). Conversely, changes in sarcoplasmic reticulum (SR) Ca 2+ handling may also cause higher diastolic Ca 2+ levels in cardiomyocytes isolated from mice with dystrophin deficiency.…”

mentioning

confidence: 99%

Genetic inhibition of PKA phosphorylation of RyR2 prevents dystrophic cardiomyopathy

Sarma

Li²,

Oort³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Aberrant intracellular Ca 2+ regulation is believed to contribute to the development of cardiomyopathy in Duchenne muscular dystrophy. Here, we tested whether inhibition of protein kinase A (PKA) phosphorylation of ryanodine receptor type 2 (RyR2) prevents dystrophic cardiomyopathy by reducing SR Ca 2+ leak in the mdx mouse model of Duchenne muscular dystrophy. mdx mice were crossed with RyR2-S2808A mice, in which PKA phosphorylation site S2808 on RyR2 is inactivated by alanine substitution. Compared with mdx mice that developed age-dependent heart failure, mdx-S2808A mice exhibited improved fractional shortening and reduced cardiac dilation. Whereas application of isoproterenol severely depressed cardiac contractility and caused 95% mortality in mdx mice, contractility was preserved with only 19% mortality in mdx-S2808A mice. SR Ca 2+ leak was greater in ventricular myocytes from mdx than mdx-S2808A mice. Myocytes from mdx mice had a higher incidence of isoproterenol-induced diastolic Ca 2+ release events than myocytes from mdx-S2808A mice. Thus, inhibition of PKA phosphorylation of RyR2 reduced SR Ca 2+ leak and attenuated cardiomyopathy in mdx mice, suggesting that enhanced PKA phosphorylation of RyR2 at S2808 contributes to abnormal Ca 2+ homeostasis associated with dystrophic cardiomyopathy.calcium | cardiomyopathy | dystrophin | ryanodine receptor | sarcoplasmic reticulum

show abstract

“…In the mdx, the limb skeletal muscle exhibits an initial periods of severe necrosis at 3-4weeks of age lifespan, however the limb muscles of mdx mice undergo sufficient muscle fiber regeneration to compensate for the continued injury to fibers and muscle fiber degeneration. Although the diaphragm muscle exhibits progressive deterioration, similar to human DMD 5,10,11 .…”

Section: Introductionmentioning

confidence: 87%

Laparoscopic guided local injection in the X-linked muscular dystrophy mouse (mdx) diaphragm. An advance in experimental therapies for Duchenne Muscular Dystrophy

Lessa

Carvalho²,

Spagnolo³

et al. 2014

Acta Cir. Bras.

View full text Add to dashboard Cite

PURPOSE:To investigate the development of a laparoscopy technique for local injection into the X-linked muscular dystrophy (mdx) diaphragm. METHODS:It was used 10 mice Balb/C57 and 5 mdx mice and three differents decubitus type were tested: the right lateral, supine, and supine decubitus with 20 degrees elevation of the forelimb. Abdominal caudal face and the 10 intercostal space were tested as spot to introduce the needle into the diaphragm. RESULTS:Supine position with elevation of 20 degrees forelimb and the 10th intercostal space are the beneficial position to apply a local injection. CONCLUSION:It was proved to be possible to perform the laparoscopy technique in the X-linked muscular dystrophy diaphragm and this requires a specific position and technique during the surgery.

show abstract

Effects of stretch‐activated channel blockers on [Ca²⁺]_i and muscle damage in the mdx mouse

Cited by 244 publications

References 56 publications

Role of dystroglycan in limiting contraction-induced injury to the sarcomeric cytoskeleton of mature skeletal muscle

Role of dystroglycan in limiting contraction-induced injury to the sarcomeric cytoskeleton of mature skeletal muscle

Genetic inhibition of PKA phosphorylation of RyR2 prevents dystrophic cardiomyopathy

Laparoscopic guided local injection in the X-linked muscular dystrophy mouse (mdx) diaphragm. An advance in experimental therapies for Duchenne Muscular Dystrophy

Contact Info

Product

Resources

About