Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.13/930339
- Amyloid-β protein impairs Ca²⁺ release and contractility in skeletal muscle
Ward, Christopher W.;
Laver, Derek R.;
Bannister, Mark L.;
Lopez, Jose R.;
LaFerla, Frank M.;
Querfurth, Henry W.
- The University of Newcastle. Faculty of Health, School of Biomedical Sciences and Pharmacy
- 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.
- Neurobiology of Aging Vol. 31, Issue 12, p. 2080-2090
- Publisher Link
inclusion body myositis;
- Resource Type
- journal article