title: Effects of a preferential myosin loss on Ca2+ activation of force generation in single human skeletal muscle fibres.
abstract: 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 Ca(2+) 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 Ca(2+) 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 Ca(2+) 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 Ca(2+) 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.
authors.affiliation: Department of Neuroscience, Clinical Neurophysiology, University Hospital, Uppsala, Sweden. julien.ochala@neurofys.uu.se
authors.forename: Julien
authors.initials: J
authors.lastname: Ochala
authors.forename: Lars
authors.initials: L
authors.lastname: Larsson
mesh_terms: D000199:Actins / Q000378:metabolism; D000208:Acute Disease; D000328:Adult; D000368:Aged; D002100:Cachexia / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism*; D016022:Case-Control Studies; D015536:Down-Regulation; D004548:Elasticity; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009119:Muscle Contraction; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology; D009135:Muscular Diseases / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D018995:Myosin Heavy Chains / Q000378:metabolism*; D011782:Quadriplegia / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors
chemical_list: D000199:Actins; D018995:Myosin Heavy Chains; D002118:Calcium