Effects of antiarrhythmic drugs on phospholipid metabolism in Jurkat T cells The potassium channel blocker, clofilium, specifically increases phosphatidylserine synthesis

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Abstract
Five antiarrhythmic drugs (bretylium, clofilium, propranolol, N-acetylprocainamide and amiodarone) were tested for their ability to modify phospholipid metabolism in Jurkat T lymphocytes. The five drugs, decreased in a dose-dependent mode the biosynthesis of both phosphatidylcholine and phosphatidylethanolamine, this effect was essentially due to impairment of either choline or ethanolamine uptake by the cells. The efficiency of the drugs to inhibit phosphatidylcholine and phosphatidylethanolamine synthesis was in the order: clofilium > amiodarone ⪢ propranolol = bretylium > N-acetylprocainamide. The IC50 varied from 3–5 μM for clofilium to >200 μM for N-acetylprocainamide. In contrast, only clofilium, a voltage-gated K+-channel blocker, was able to increase phosphatidylserine synthesis with an EC50 = 50 μM. The effect of clofilium on phosphatidylserine synthesis thus mimics the effect of three other K+-channel blockers, quinine, 4-aminopyridine and tetraethylammonium, suggesting close relationships between phosphatidylserine synthesis and K+ channel activity.