Intracellular β-amyloid accumulation leads to age-dependent progression of Ca2+ dysregulation in skeletal muscle

Josè R. Lopez, Alexander Shtifman

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Intramyofiber accumulation of β-amyloid fragments (Aβ) is a pathologic hallmark of inclusion-body myositis (IBM), a progressive skeletal muscle disorder. We investigated the temporal pattern of alterations in the resting cytoplasmic [Ca2+] ([Ca2+]i) as well as the depolarization-evoked Ca2+ release from the sarcoplasmic reticulum in skeletal muscle from transgenic mice expressing human βAPP (MCK-βAPP). MCK-βAPP mice show an age-dependent increase in [Ca 2+]i along with a reduction in depolarization-evoked Ca2+ release, which appear well before the other reported aspects of IBM, such as inclusion formation, inflammation, centralized nuclei, atrophy, and skeletal muscle weakness. In the young MCK-βAPP animals the increase in resting [Ca2+]i can be attributed largely to Ca 2+ influx through nifedipine-sensitive Ca2+ channels. In the adult MCK-βAPP mice, in addition to the nifedipine-sensitive pathway, there is also a substantial contribution by the intracellular compartments to the increase in [Ca2+]i. These results suggest that β-amyloid-induced disuption of Ca2+ handling may represent an early event in the pathogenesis of IBM.

Original languageEnglish (US)
Pages (from-to)731-738
Number of pages8
JournalMuscle and Nerve
Volume42
Issue number5
DOIs
StatePublished - Nov 2010
Externally publishedYes

Keywords

  • β-amyloid
  • Amyloid precursor protein
  • Calcium
  • Calcium influx
  • Inclusion-body myositis
  • L-type Ca channels
  • Muscle
  • Ryanodine receptors

ASJC Scopus subject areas

  • Physiology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Physiology (medical)

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