Phosphatidic acid regulates the activity of the channel-forming ionophores alamethicin, melittin, and nystatin: A¹H-NMR study using phospholipid membranes

The regulation of ion channels by phosphatidic acid (a proposed active metabolite in the phosphatidylinositol effect) was investigated using¹H-NMR spectroscopy and small unilamellar phospholipid vesicles. Transport across egg-yolk phosphatidylcholine (egg PC) and dipalmitoyl phosphatidylcholine (DPPC) vesicular membranes in the presence of the channel-forming ionophores alamethicin, melittin, and nystatin was monitored using the lanthanide probe ion Pr³⁺. In the absence of the ionophores, phosphatidic acid (PA) alone was found to have no ionophore properties, but in the presence of the ionophores the incorporation of 3 mol % phosphatidic acid in the bilayer markedly increased the rate of transport using melittin and nystatin, but decreased the rate using alamethicin, independent of the type of phosphatidylcholine used. The presence of PA in the bilayer also stimulated the production of lyric type channels, the extent of which were both ionophore- and lipid-dependent. These results are discussed in terms of possible molecular interactions between the PA, the individual ionophores, and type of lipid used.