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This Article Full Text Full Text (PDF) All Versions of this Article: 93/4/486    most recent expphysiol.2007.041798v1 Alert me when this article is cited Alert me if a correction is posted 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 Google Scholar Articles by Ochala, J. Articles by Larsson, L. PubMed PubMed Citation Articles by Ochala, J. Articles by Larsson, L.

¹Department of Clinical Neurophysiology, Uppsala University Hospital, Uppsala, Sweden ²Center for Development and Health Genetics, The Pennsylvania State University, University Park, PA, USA

Preferential loss of the motor protein myosin, as observed in patients with acute quadriplegic myopathy (AQM) or cancer cachexia, causes generalized muscle wasting, muscle weakness and a decrease in muscle fibre force normalized to cross-sectional area. It remains unclear, however, whether this myosin loss influences other important features of muscle fibre function, such as Ca²⁺ activation of the contractile proteins. To address this question, we have studied Ca²⁺ sensitivity of force generation using skinned muscle fibres from four patients with AQM or cancer cachexia and a preferential loss of myosin; and from seven healthy control individuals. Force and apparent rate constant of force redevelopment (k_tr) were assessed in solutions with varying Ca²⁺ concentrations (pCa), allowing construction of relative force–pCa and k_tr–pCa relationships. Results showed a rightward shift of the relative force–pCa relationship and a leftward shift of the relative k_tr–pCa curve in muscle fibres with a preferential myosin loss. To improve the understanding of the mechanisms underlying these alterations, the relative stiffness–pCa relationship was evaluated. A rightward shift of this curve was observed, suggesting that the changes in the Ca²⁺ activation of force and k_tr were predominantly due to a decrease in the relative number of attached cross-bridges at different pCa values. Thus, a change in Ca²⁺ activation of the contractile apparatus in patients with preferential myosin loss is proposed as an additional factor contributing to the muscle function impairment in these patients.

(Received 17 December 2007; accepted after revision 28 January 2008; first published online 1 February 2008)
Corresponding author J. Ochala: Department of Neuroscience, Clinical Neurophysiology, University Hospital, Entrance 85, 3rd floor, SE-751 85 Uppsala, Sweden. Email: julien.ochala{at}neurofys.uu.se