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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Abnormal sarcoplasmic reticulum Ca²⁺-sequestering properties in skeletal muscle in chronic obstructive pulmonary disease

¹Department of Kinesiology, University of Waterloo, Waterloo, Ontario; and ²Division of Respiratory and Critical Care Medicine, Department of Medicine, Queen's University, Kingston, Ontario, Canada

Submitted 24 April 2008 ; accepted in final form 24 May 2008

The objective of this study was to investigate the hypothesis that alterations in sarcoplasmic reticulum (SR) Ca²⁺-cycling properties would occur in skeletal muscle in patients with moderate to severe chronic obstructive pulmonary disease (COPD). To investigate this hypothesis, tissue samples were obtained from the vastus lateralis of 8 patients with COPD [age 65.6 ± 3.2 yr; forced expiratory volume in 1 s (FEV₁)/forced vital capacity (FVC) = 44 ± 2%; mean ± SE] and 10 healthy age-matched controls (CON, age 67.5 ± 2.5 yr; FEV₁/FVC = 77 ± 2%), and homogenates were analyzed for a wide range of SR properties. Compared with CON, COPD displayed (in µmol·g protein^–1·min^–1) a 16% lower maximal Ca²⁺-ATPase activity [maximal velocity (V_max), 158 ± 10 vs. 133 ± 7, P < 0.05] and a 17% lower Ca²⁺ uptake (4.65 ± 0.039 vs. 3.85 ± 0.26, P < 0.05) that occurred in the absence of differences in Ca²⁺ release. The lower V_max in COPD was also accompanied by an 11% lower (P < 0.05) Ca²⁺ sensitivity, as measured by the Hill coefficient (defined as the relationship between Ca²⁺-ATPase activity and free cytosolic Ca²⁺ concentration for 10–90% V_max). For the sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA) isoforms, SERCA1a was 16% higher (P < 0.05) and SERCA2a was 14% lower (P < 0.05) in COPD. It is concluded that moderate to severe COPD results in abnormalities in SR Ca²⁺-ATPase properties that cannot be explained by changes in the SERCA isoform phenotypes. The reduced catalytic properties of SERCA in COPD suggest a disturbance in Ca²⁺ cycling, possibly resulting in impairment in Ca²⁺-mediated mechanical function and/or second messenger regulated processes.

skeletal muscle; lung disease; sarcoplasmic reticulum; calcium regulation

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