AJP - Heart and Circulatory Physiology, Vol 256, Issue 2 368-H374, Copyright © 1989 by American Physiological Society
Depression of heart sarcolemmal Ca2+-pump activity by oxygen free radicals
M. Kaneko, R. E. Beamish and N. S. Dhalla
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Canada.
Although oxygen free radicals have been implicated as mediators of cellular
injury in myocardial ischemia-reperfusion, the exact nature of defects
produced by these radicals is not clear. Because sarcolemmal Ca2+-pump is
involved in the efflux of Ca2+ from the cell, this study was undertaken to
examine the effects of oxygen free radicals on sarcolemmal ATP-dependent
Ca2+ accumulation and Ca2+-stimulated Mg2+-dependent
adenosinetriphosphatase (ATPase) activities as well as lipid peroxidation
of membrane phospholipids. Isolated rat heart sarcolemmal membranes were
incubated with xanthine + xanthine oxidase [a superoxide anion radical
(O2-)-generating system], H2O2, or H2O2 + Fe2+ [a hydroxyl radical
(HO.)-generating system] and assayed for Ca2+-pump activities. O2-
inhibited the Ca2+-pump activities in a time-dependent manner; a
significant inhibition of Ca2+-stimulated ATPase activity was seen after 1
min of incubation. Superoxide dismutase showed a protective effect on
depression in Ca2+-pump activities caused by O2-.H2O2 inhibited Ca2+-pump
activities in a dose-dependent manner; this inhibition was protected by the
addition of catalase. HO. depressed the Ca2+-pump activities to a greater
extent in comparison with H2O2. Mannitol showed a protective effect on
HO.-induced inhibition of Ca2+-pump activities. The promotion of lipid
peroxidation by free radicals was evident from increased formation of
malondialdehyde. These results indicate that the sarcolemmal membrane is
altered on exposure to oxygen free radicals, and this may result in
depressing the Ca2+-pump mechanism for Ca2+ efflux from the myocardial
cell.
