Abnormal sarcoplasmic reticulum Ca2+-sequestering properties in skeletal muscle in chronic obstructive pulmonary disease.
The objective of this study was to investigate the hypothesis that alterations in sarcoplasmic reticulum (SR) Ca(2+)-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 (FEV(1))/forced vital capacity (FVC) = 44 +/- 2%; mean +/- SE] and 10 healthy age-matched controls (CON, age 67.5 +/- 2.5 yr; FEV(1)/FVC = 77 +/- 2%), and homogenates were analyzed for a wide range of SR properties. Compared with CON, COPD displayed (in mumol.g protein(-1).min(-1)) a 16% lower maximal Ca(2+)-ATPase activity [maximal velocity (V(max)), 158 +/- 10 vs. 133 +/- 7, P < 0.05] and a 17% lower Ca(2+) uptake (4.65 +/- 0.039 vs. 3.85 +/- 0.26, P < 0.05) that occurred in the absence of differences in Ca(2+) release. The lower V(max) in COPD was also accompanied by an 11% lower (P < 0.05) Ca(2+) sensitivity, as measured by the Hill coefficient (defined as the relationship between Ca(2+)-ATPase activity and free cytosolic Ca(2+) concentration for 10-90% V(max)). For the sarco(endo)plasmic reticulum Ca(2+)-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 Ca(2+)-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 Ca(2+) cycling, possibly resulting in impairment in Ca(2+)-mediated mechanical function and/or second messenger regulated processes.
Dept. of Kinesiology, Univ. of Waterloo, Waterloo, On, Canada, N2L3G1. green@healthy.uwaterloo.ca
H J
HJ
Green
M
M
Burnett
T A
TA
Duhamel
C
C
D'Arsigny
D E
DE
O'Donnell
K A
KA
Webb
J
J
Ouyang
D000368:Aged; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D002245:Carbon Dioxide / Q000097:blood; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008168:Lung / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism*; D010100:Oxygen / Q000097:blood; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D052097:Quadriceps Muscle / Q000201:enzymology / Q000378:metabolism; D012129:Respiratory Function Tests; D012519:Sarcoplasmic Reticulum / Q000201:enzymology / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000737:chemistry / Q000378:metabolism*; D014797:Vital Capacity / Q000502:physiology
D007527:Isoenzymes; D002245:Carbon Dioxide; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506943:ATP2A1 protein, human; C506946:ATP2A2 protein, human; D010100:Oxygen; D002118:Calcium