Altered myofilament function depresses force generation in patients with nebulin-based nemaline myopathy (NEM2).

ABSTRACT: Nemaline myopathy (NM), the most common non-dystrophic congenital myopathy, is clinically characterized by muscle weakness. However, the mechanisms underlying this weakness are poorly understood. Here, we studied the contractile phenotype of skeletal muscle from NM patients with nebulin mutations (NEM2). SDS-PAGE and Western blotting studies revealed markedly reduced nebulin protein levels in muscle from NM patients, whereas levels of other thin filament-based proteins were not significantly altered. Muscle mechanics studies indicated significantly reduced calcium sensitivity of force generation in NM muscle fibers compared to control fibers. In addition, we found slower rate constant of force redevelopment, as well as increased tension cost, in NM compared to control fibers, indicating th

SUBMITTER: Ottenheijm CA 

PROVIDER: S-EPMC2856782 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature