Effects of a preferential myosin loss on Ca2+ activation of force generation in single human skeletal muscle fibres
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Effects of a preferential myosin loss on Ca2+ activation of force generation in single human skeletal muscle fibres. / Ochala, Julien; Larsson, Lars.
In: Experimental Physiology, Vol. 93, No. 4, 04.2008, p. 486-495.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Effects of a preferential myosin loss on Ca2+ activation of force generation in single human skeletal muscle fibres
AU - Ochala, Julien
AU - Larsson, Lars
PY - 2008/4
Y1 - 2008/4
N2 - 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 Ca 2+ 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 Ca 2+ 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.
AB - 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 Ca 2+ 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 Ca 2+ 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.
UR - http://www.scopus.com/inward/record.url?scp=40849140970&partnerID=8YFLogxK
U2 - 10.1113/expphysiol.2007.041798
DO - 10.1113/expphysiol.2007.041798
M3 - Journal article
C2 - 18245202
AN - SCOPUS:40849140970
VL - 93
SP - 486
EP - 495
JO - Experimental Physiology
JF - Experimental Physiology
SN - 0958-0670
IS - 4
ER -
ID: 245665402