AJP - Cell Physiology, Vol 259, Issue 2 C325-C331, Copyright © 1990 by American Physiological Society
Selective turnover of sarcolemmal phospholipids with lethal cardiac myocyte injury
Y. Miyazaki, R. W. Gross, B. E. Sobel and J. E. Saffitz
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
To delineate the biochemical mechanisms responsible for the transition from
reversible to irreversible ischemic injury, we used quantitative electron
microscopic autoradiography. Specific alterations of phospholipid
catabolism in individual subcellular organelles of cardiac myocytes
associated with simulated ischemic injury were identified. Neonatal rat
cardiac myocytes were incubated with 5 nM [3H]arachidonic acid to label
loci of phospholipid turnover and were exposed to 30 microM iodoacetate to
produce reversible and irreversible injury. Although only minute amounts of
arachidonic acid were incorporated into sarcolemmal phospholipids under
control conditions, 20- and 96-fold increases were observed under
conditions leading to reversible and irreversible cell injury,
respectively. Increases of 5- and 28-fold in the specific radioactivity of
sarcolemmal phospholipids in reversibly and irreversibly injured cells
occurred in the absence of significant alterations in the specific
radioactivity of other subcellular compartments, demonstrating that
accelerated phospholipid catabolism was confined essentially to the
sarcolemma. Selective catabolism of sarcolemmal phospholipids, known to be
highly enriched in arachidonic acid, is likely to augment local
accumulation of arachidonic acid, identified recently as a second messenger
regulating myocardial K+ channels. Because the biochemical integrity of the
sarcolemma is critical to both electrophysiological function and viability
of myocytes, the observed selective alterations of sarcolemmal phospholipid
metabolism appear to be pivotal determinants of lethal myocardial injury.
