Organization and function of sarcolemmal phospholipids in control and ischemic/reperfused cardiomyocytes.

The topic of this review is the lipidic part of the sarcolemma, the plasma membrane of the myocardial cell, and its role in (dis)function of the cardiomyocyte. First the isolation of the sarcolemma and its lipid composition are discussed. These phospholipids are not randomly distributed over the two monolayers of the lipid bilayer and negatively charged phospholipids are exclusively present in the cytoplasmic leaflet of the sarcolemma, which also contains the majority of phosphatidylethanolamine. This distribution is most likely caused by an active transport of these lipids and by an interaction of the headgroup of these lipids with the cytoskeleton. Subsequently the physicochemical properties of sarcolemmal phospholipids are discussed, where it is shown that certain phospholipids prefer non-bilayer phases, and the effects of sarcolemmal phospholipids on trans-sarcolemmal ion fluxes and calcium compartmentation are discussed. In the second part the effect of ischemia on sarcolemmal phospholipids is discussed with regard to: transbilayer distribution, hydrolysis, lateral distribution and sarcolemmal bilayer stability. In our view, onset of ischemia initiates a sequence of events leading to a loss of normal sarcolemmal phospholipid distribution with an outward migration of phosphatidylethanolamine. There follows, as ischemia progresses, loss of sarcolemmal bilayer stability due to the expression of the non-bilayer behavior of phosphatidylethanolamine, leading to irreversible disruption of the sarcolemma and cell death.