Inhibition of Na⁺–Ca²⁺ exchange in heart sarcolemmal vesicles by phosphatidylethanolamine N‐methylation

The effect of phosphatidylethanolamine N ‐methylation on Na + ‐Ca 2+ exchange was studied in sarcolemmal vesicles isolated from rat heart. Phosphatidylethanolamine N ‐methylation following incubation of membranes with S ‐adenosyl‐ l ‐methionine, a methyl donor for the enzymatic N ‐methylation, inhibited Na + i ‐dependent Ca 2+ uptake by about 50%. The N ‐methylation reaction did not alter the passive permeability of the sarcolemmal vesicles to Na + and i ‐dependent Ca 2+ uptake by about 50%. The N ‐methylation reaction did not alter the passive permeability of the sarcolemmal vesicles to Na + and Ca 2+ and did not modify the electrogenic characteristics of the exchanger. The depressant effect of phosphatidylethanolamine N ‐methylation on Na + i ‐dependent Ca 2+ uptake was prevented by S ‐adenosyl‐ l ‐homocysteine, an inhibitor of the N ‐methylation. Pretreatment of sarcolemma with methyl acetimidate hydrochloride, an amino‐group‐blocking agent, also prevented methylation‐induced inhibition of Ca 2+ uptake. In the presence of exogenous phospholipid substrate, the phospholipid N ‐methylation process in methyl‐acetimidate‐presence of exogenous phospholipid substrate, the phospholipid N ‐methylation process in methyl‐acetimidate‐treated sarcolemmal vesicles was restored and the inhibitory effect on Ca 2+ uptake was evident. These results suggest that phosphatidylethanolamine N ‐methylation influences the heart sarcolemmal Na + ‐Ca 2+ exchange system.