Selective turnover of sarcolemmal phospholipids with lethal cardiac myocyte injury

Y. Miyazaki, R. W. Gross, B. E. Sobel, J. E. Saffitz

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26 Scopus citations

Abstract

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 μM 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.

Original languageEnglish
Pages (from-to)C325-C331
JournalAmerican Journal of Physiology - Cell Physiology
Volume259
Issue number2 28-3
DOIs
StatePublished - Jan 1 1990

Keywords

  • Arachidonic acid
  • Electron microscopic autoradiography
  • Iodoacetate
  • Myocardial ischemia
  • Neonatal rat cardiac myocytes

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