On the possible role of long chain fatty acylcarnitine accumulation in producing functional and calcium permeability changes in membranes during myocardial ischaemia

A radioisotope procedure was used to determine long chain fatty acylcarnitine concentrations in fractions of porcine myocardium that had been subjected to different periods of ischaemia (0, 1, 2, and 3 h). In myocardial tissue from non-ligated hearts acylcarnitine concentrations were 0.32(0.03) and 1.53(0.04) nmol·mg-1 protein for homogenate and sarcolemma enriched membrane respectively, which indicates a preferential membrane localisation of long chain fatty acylcarnitine. Both the total and membrane acylcarnitine contents were increased about twofold after 2 h of ischaemia. The accumulation of long chain fatty acylcarnitine was not correlated temporally with changes in adenosine triphosphate dependent calcium uptake activity of homogenates (mainly a function of sarcoplasmic reticulum membranes), sodium gradient induced calcium uptake, and calcium permeability of sarcolemma preparations. Homogenate adenosine triphosphate dependent calcium uptake was decreased by 36% after 3 h of ischaemia. Sodium gradient induced calcium uptake was enhanced about twofold after 1 h of ischaemia, and calcium permeability of sarcolemmal vesicles was decreased by 20% after 3 h of ischaemia. After in vitro incubation of isolated sarcolemma membranes with (l-14C)-palmitoylcarnitine radiolabeled molecules that remained associated with the membrane even after repeated washing were incorporated. No changes were observed in the sodium gradient induced calcium uptake when <6 nmol (l-l4C)-palmitoylcarnitine per mg sarcolemma protein were bound or incorporated into the lipid phase. This exceeded the maximal endogenous concentrations of 3.2(0.6) nmol long chain fatty acylcarnitine per mg sarcolemma protein observed during myocardial ischaemia. The results suggest that the intracellular increase in long chain acylcarnitine during almost zero myocardial flow is not critical to sarcolemmal sodium and calcium permeability and sarcoplasmic reticulum calcium pumping activity.

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