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MUSCLE CELL BIOLOGY AND CELL MOTILITY

Ultrastructural remodeling of fast skeletal muscle fibers induced by invalidation of creatine kinase

Marta Novotová,¹ Michaela Pavloviová,¹ Vladimir I. Veksler,² Renée Ventura-Clapier,² and Ivan Zahradník¹

¹Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Bratislava, Slovak Republic; ²Institut National de la Santé et de la Recherche Médicale Unité 769, Signalisation et Physiophatologie Cardiac, Faculté de Pharmacie, Université Paris-Sud, Châtenay-Malabry, France

Submitted 14 May 2006 ; accepted in final form 14 July 2006

Understanding muscle adaptation to various stimuli is difficult because of the complex nature of stimuli and responses. In particular, responses to perturbations in energy metabolism require careful examination, because they may involve both structural and functional elements. To estimate the structural component of the myocyte adaptation to energetic deficiency, we used transgenic mice with blocked expression of mitochondrial and cytosolic creatine kinases (CK). The ultrastructure was analyzed using the stereological method of vertical sections applied to electron microscopic images of ultrathin longitudinal sections of fast muscle fibers of gastrocnemius, known to adapt to CK deficiency by increasing oxidative metabolism. The lack of CK induced a profound structural adaptation response that included changes in the volume and surface densities of major organelles. In addition, using a new stereological parameter, the environment of an organelle, substantial changes in the mitochondrial neighborhood were identified pointing to their relocation closer to the major sites of energy consumption, supposedly to compensate for invalidated energy transfer. Using quantitative arguments, we have shown for the first time that spatial relations among organelles of muscle cells undergo adaptation in response to nonstructural stimuli like metabolic deficiency.

skeletal muscle cells; structure; adaptation; energy deficiency

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