Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.13/930339

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Title
Amyloid-β protein impairs Ca²⁺ release and contractility in skeletal muscle
Author/Creator
Shtifman, Alexander;  Ward, Christopher W.;  Laver, Derek R.;  Bannister, Mark L.;  Lopez, Jose R.;  Kitazawa, Masashi;  LaFerla, Frank M.;  Ikemoto, Noriaki;  Querfurth, Henry W.
Institution
The University of Newcastle. Faculty of Health, School of Biomedical Sciences and Pharmacy
Description
Inclusion body myositis (IBM), the most common muscle disorder in the elderly, is partly characterized by dysregulation of β-amyloid precursor protein (βAPP) expression and abnormal, intracellular accumulation of full-length βAPP and β-amyloid epitopes. The present study examined the effects of β-amyloid accumulation on force generation and Ca²⁺ release in skeletal muscle from transgenic mice harboring human βAPP and assessed the consequence of Aβ₁₋₄₂ modulation of the ryanodine receptor Ca²⁺ release channels (RyRs). β-Amyloid laden muscle produced less peak force and exhibited Ca²⁺ transients with smaller amplitude. To determine whether modification of RyRs by β-amyloid underlie the effects observed in muscle, in vitro Ca²⁺ release assays and RyR reconstituted in planar lipid bilayer experiments were conducted in the presence of Aβ₁₋₄₂. Application of Aβ₁₋₄₂ to RyRs in bilayers resulted in an increased channel open probability and changes in gating kinetics, while addition of Aβ₁₋₄₂ to the rabbit SR vesicles resulted in RyR-mediated Ca²⁺ release. These data may relate altered βAPP metabolism in IBM to reductions in RyR-mediated Ca²⁺ release and muscle contractility.
Relation
Neurobiology of Aging Vol. 31, Issue 12, p. 2080-2090
Publisher Link
http://dx.doi.org/10.1016/j.neurobiolaging.2008.11.003
Date
2010
Publisher
Elsevier
Keyword(s)
inclusion body myositis;  β-Amyloid;  βAPP;  ryanodine receptors;  excitation–contraction coupling
Resource Type
journal article
Identifier
http://hdl.handle.net/1959.13/930339
Identifier
ISSN:0197-4580
Reviewed
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Subject
"Neurobiology of Aging"
 
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