| First Author | Shtifman A | Year | 2010 |
| Journal | Neurobiol Aging | Volume | 31 |
| Issue | 12 | Pages | 2080-90 |
| PubMed ID | 19108934 | Mgi Jnum | J:168296 |
| Mgi Id | MGI:4887554 | Doi | 10.1016/j.neurobiolaging.2008.11.003 |
| Citation | Shtifman A, et al. (2010) Amyloid-beta protein impairs Ca(2+) release and contractility in skeletal muscle. Neurobiol Aging 31(12):2080-90 |
| abstractText | Inclusion body myositis (IBM), the most common muscle disorder in the elderly, is partly characterized by dysregulation of beta-amyloid precursor protein (betaAPP) expression and abnormal, intracellular accumulation of full-length betaAPP and beta-amyloid epitopes. The present study examined the effects of beta-amyloid accumulation on force generation and Ca(2+) release in skeletal muscle from transgenic mice harboring human betaAPP and assessed the consequence of Abeta(1-42) modulation of the ryanodine receptor Ca(2+) release channels (RyRs). beta-Amyloid laden muscle produced less peak force and exhibited Ca(2+) transients with smaller amplitude. To determine whether modification of RyRs by beta-amyloid underlie the effects observed in muscle, in vitro Ca(2+) release assays and RyR reconstituted in planar lipid bilayer experiments were conducted in the presence of Abeta(1-42). Application of Abeta(1-42) to RyRs in bilayers resulted in an increased channel open probability and changes in gating kinetics, while addition of Abeta(1-42) to the rabbit SR vesicles resulted in RyR-mediated Ca(2+) release. These data may relate altered betaAPP metabolism in IBM to reductions in RyR-mediated Ca(2+) release and muscle contractility. |
