The effects of exposure to exogenous fatty acids and membrane fatty acid modification on the electrical properties of NG108-15 cells

1. The role of membrane lipid composition in determining the electrical properties of neuronal cells was investigated by altering the available fatty acids in the growth medium of cultured neuroblastoma × glioma hybrid cells, clone NG108-15. 2. Growth of the cells for several days in the presence of polyunsaturated fatty acids (linoleic, linolenic, and arachidonic) caused a pronounced decrease in the Na⁺ action-potential rate of rise (dV/dt) and smaller decreases in the amplitude, measured by intracellular recording. Oleic acid had no effect on the action potentials generated by the cells. In contrast, a saturated fatty acid (palmitate) and a trans monounsaturated fatty acid (elaidate) caused increases in both the rate of rise and the amplitude. 3. No changes in the resting membrane potentials or Ca²⁺ action potentials of fatty acid-treated cells were observed. The membrane capacitance and time constant were not altered by exposure to arachidonate, oleate, or elaidate, whereas arachidonate caused a small increase in membrane resistance. 4. Examination of the membrane phospholipid fatty acid composition of cells grown with various fatty acids revealed no consistent alterations which could explain these results. 5. To examine the mechanism for arachidonate-induced decreases in dV/dt, the binding of³H-saxitoxin (known to interact with voltage-sensitive Na⁺) channels was measured. Membranes from cells grown with arachidonate contained fewer saxitoxin binding sites, suggesting fewer Na⁺ channels in these cells. 6. We conclude that conditions which lead to major changes in the membrane fatty acid composition have no effect on the resting membrane potential, membrane capacitance, time constant, or Ca²⁺ action potentials in NG108-15 cells. Membrane resistance also does not appear to be very sensitive to membrane fatty acid composition. However, changes in the availability of fatty acids and/or changes in the subsequent membrane fatty acid composition lead to altered Na⁺ action potentials. The primary mechanism for this alteration appears to be through changes in the number of Na⁺ channels in the cells.