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 -