PHOSPHATIDYLETHANOLAMINE AND SARCOLEMMAL DAMAGE DURING ISCHEMIA OR METABOLIC INHIBITION OF HEART MYOCYTES

Phosphatidylethanolamine (PE) is a nonbilayer-preferring and fusogenic phospholipid. It is kept in the bilayer configuration by interaction with other phospholipids in biologic membranes. However, reorganizatio n of the membrane phospholipids could lead to expression of the nonbil ayer nature of PE and induce bilayer instability. During ischemia a tr ansbilayer reorganization of sarcolemmal PE is observed, and results h ave been published that suggest a lateral phase separation in the inne r sarcolemmal leaflet phospholipids. These reorganizations and the sub sequent expression of the nonbilayer behavior of PE are proposed to fo rm the basis for sarcolemma destabilization and destruction. Lowering the PE content of myocytes, especially of the sarcolemma, is then expe cted to attenuate myocyte damage after simulated ischemia or metabolic inhibition. Culturing neonatal rat heart myocytes in the presence of N,N-dimethylethanolamine resulted in the synthesis of the bilayer-pref erring N,N-dimethyl-PE and a lowering of the ratio between nonbilayer- and bilayer-preferring phospholipids from 0.58 to 0.30. This change i n phospholipid composition did not impair cell functioning but did res ult in a strong attenuation of cell damage on ischemia or metabolic in hibition. A good correlation between the nonbilayer-preferring phospho lipid content and the degree of cell damage was obtained (r = 0.98). T hese results provide further evidence that physicochemical properties of the sarcolemmal phospholipids play a crucial role in the sarcolemma l disruption during prolonged ischemia and/or reperfusion.