Arachidonic Acid and Other Unsaturated Fatty Acids Alter Membrane Potential in PC12 and Bovine Adrenal Chromaffin Cells

Abstract: The action of arachidonic acid and other fatty acids on membrane potential in PC 12 and bovine chromaffin cells was investigated using a membrane potential-sensitive fluorescent dye. Arachidonic acid (1–40 μ M ) provoked dose-dependent membrane hyperpolarization, thereby reducing hyperpolarization induced by the K⁺-selective ionophore valinomycin. Other cis-unsaturated fatty acids, but not lipoxygenase products or the saturated fatty acid palmitic acid, also affected membrane potential. Tetraethylammonium blocked the arachidonic acid-induced hyperpolarization. These data suggest that cis-unsaturated fatty acids alter membrane potential in PC 12 and bovine chromaffin cells by modulating K⁺ conductances. Valinomycin-generated hyperpolarization had no effect on agonist-induced Ca²⁺ influx into bovine chromaffin cells, whereas preincubation with arachidonic acid and other cis-unsaturated fatty acids blocked Ca²⁺ influx and secretion. We propose a model where internally generated fatty acids act as a feed-back to desensitize the stimulated cell via inhibition of receptor-dependent Ca²⁺ influx and induction of membrane hyperpolarization.