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This Article Full Text Full Text (PDF) All Versions of this Article: 577/1/339    most recent jphysiol.2006.116749v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Olsson, M. C. Articles by Larsson, L. Search for Related Content PubMed PubMed Citation Articles by Olsson, M. C. Articles by Larsson, L. Related Collections Skeletal Muscle and Exercise

Uppsala University, Department of Neuroscience,
¹ Clinical Neurophysiology
³ Rehabilitation Medicine, 75185 Uppsala, Sweden
² University of Münster, Physiology and Biophysics Unit, 48149 Münster, Germany
⁴ Center for Development and Health Genetics, The Pennsylvania State University, University Park, PA 16802, USA

Patients with spasticity typically present with an increased muscle tone that is at least partly caused by an exaggerated stretch reflex. However, intrinsic changes in the skeletal muscles, such as altered mechanical properties of the extracellular matrix or the cytoskeleton, have been reported in response to spasticity and could contribute to hypertonia, although the underlying mechanisms are poorly understood. Here we examined the vastus lateralis muscles from spinal cord-injured patients with spasticity (n = 7) for their passive mechanical properties at three different levels of structural organization, in comparison to healthy controls (n = 7). We also assessed spasticity-related alterations in muscle protein expression and muscle ultrastructure. At the whole-muscle level in vivo, we observed increased passive tension (PT) in some spasticity patients particularly at long muscle lengths, unrelated to stretch reflex activation. At the single-fibre level, elevated PT was found in cells expressing fast myosin heavy chain (MyHC) isoforms, especially MyHC-IIx, but not in those expressing slow MyHC. Type IIx fibres were present in higher than normal proportions in spastic muscles, whereas type I fibres were proportionately reduced. At the level of the isolated myofibril, however, there were no differences in PT between patients and controls. The molecular size of the giant protein titin, a main contributor to PT, was unchanged in spasticity, as was the titin : MyHC ratio and the relative desmin content. Electron microscopy revealed extensive ultrastructural changes in spastic muscles, especially expanded connective tissue, but also decreased mitochondrial volume fraction and appearance of intracellular amorphous material. Results strongly suggest that the global passive muscle stiffening in spasticity patients is caused to some degree by elevated PT of the skeletal muscles themselves. We conclude that this increased PT component arises not only from extracellular matrix remodelling, but also from structural and functional adaptations inside the muscle cells, which alter their passive mechanical properties in response to spasticity in a fibre type-dependent manner.

(Received 7 July 2006; accepted after revision 21 August 2006; first published online 24 August 2006)
Corresponding authors W. A. Linke: Physiology and Biophysics Unit, University of Münster, Schlossplatz 5, D-48149 Münster, Germany; L. Larsson: Department of Neuroscience, Clinical Neurophysiology, Uppsala University, Ing 85, 3 tr., 751 85 Uppsala, Sweden.  Email: wlinke{at}uni-muenster.de or lars.larsson{at}neurofys.uu.se