Received December 17, 2007
Revised January 11, 2008
Accepted after revision January 28, 2008

¹ Uppsala University

^* To whom correspondence should be addressed. E-mail: julien.ochala{at}neurofys.uu.se.

	Abstract

Preferential loss of the motor protein myosin, as observed in patients with acute quadriplegic myopathy (AQM) and 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 (ktr) were assessed in solutions with varying Ca2+ concentrations (pCa), allowing construction of relative force-pCa and ktr-pCa relationships. Results showed a rightward shift of the relative force-pCa relationship and a leftward shift of the relative ktr-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 ktr 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.

Key Words: Muscle contraction, Muscle fibre, Myosin