The functional role of ahnak in skeletal muscle fibers in an ahnak knock-out-mouse model

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Ahnak is a muscle protein that may be involved in plasmalemma enlargement and membrane repair. The aim of the proposed project is the elucidation of ahnak's role in skeletal muscle cells and tissue. Recently, we demonstrated that in cardiomyocytes ahnak is associated with the regulation of the L-Type Ca2+ channel activity and therefore, excitation-contraction coupling, as well as the cell's structural integrity. However, the functional role of ahnak in skeletal muscle is unclear. Preliminary results suggest that skeletal muscle atrophy induced by denervation significantly upregulated ahnak expression. Therefore, we will first identify ahnak interaction partners in skeletal muscle, in particular the L-type Ca2+ channel and dysferltn, by immuno-precipitation and MALDI-TOFF analysis. Second, we will analyze the functional role of ahnak using a homozygous ahnak gene-deficient mouse model (contraction and intracellular Ca2+ in skeletal muscle registration of intact single skeletal muscle fibers from Flexor digitorum brevis of mouse hindlimb). Third, we wili analyze the functional (simultaneous registration of contraction and intracellular Ca2+) and structural (electron microscopy) role of ahnak in atrophic muscle induced by hindlimb immobilization of normal and ahnak gene-deficient mice.