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

Abstract

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 ( Vmax), 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 Vmaxin 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% Vmax). 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.