Abnormal Membrane Localization of [alpha]2 Isoform of Na,K-ATPase in m. soleus of Dysferlin-Deficient Mice

Dysferlin protein plays a key role in the multimolecular complex responsible for the maintenance of sarcolemma integrity and skeletal muscle cell functioning. We studied the membrane distribution of nicotinic acetylcholine receptors and [alpha]2 isoform of Na,K-ATPase in motor endplates of m. soleus in dysferlin-deficient Bla/J mice (a dysferlinopathy model). Endplates of Bla/J mice were characterized by increased area (without changes in fragmentation degree) and reduced density of the membrane distribution of nicotinic acetylcholine receptors in comparison with the corresponding parameters in control C57Bl/6 mice. The density of the membrane distribution of [alpha]2 isoform of Na,K-ATPase was also reduced, but the level of the corresponding mRNA remained unchanged. It can be hypothesized that abnormal membrane localization of [alpha]2 isoform of Na,K-ATPase results from adaptive skeletal muscle remodeling under conditions of chronic motor dysfunction. Key Words: skeletal muscle; dysferlin; dysferlinopathy; Na,K-ATPase isoforms; nicotinic acetylcholine receptors