ARACHIDONIC-ACID ACTIVATION OF A NEW FAMILY OF K+ CHANNELS IN CULTURED RAT NEURONAL CELLS

1. The presence and properties of K+ channels activated by arachidonic acid were studied in neuronal cells cultured from the mesencephalic a nd hypothalamic areas of rat brain. 2. Arachidonic acid produced a con centration-dependent (5-50 mu M) and reversible activation of whole-ce ll currents. 3. In excised membrane patches, arachidonic acid applied to the cytoplasmic or extracellular side of the membrane caused openin g of three types of channels whose current-voltage relationships were slightly outwardly rectifying, inwardly rectifying and linear, and who se single channel slope conductances at +60 mV were 143, 45 and 52 pS, respectively. 4. All three currents were K+ selective and blocked by 2 mM Ba2+ but not by other K+ channel blockers such as tetraethylammon inm chloride, 4-aminopyridine and quinidine. The outwardly and inwardl y rectifying currents were slightly voltage dependent with higher chan nel activity at more depolarized potentials. 5. Arachidonic acid activ ated the K+ channels in cells treated with cyclo-oxygenase and lipoxyg enase inhibitors (indomethacin and nordihydroguaiaretic acid), indicat ing that arachidonic acid itself can directly activate the channels. A lcohol and methyl ester derivatives of arachidonic acid failed to acti vate the K+ channels, indicating that the chars ed carboxyl group is i mportant for activation. bbbb 6. Certain unsaturated fatty acids (lino leic, linolenic and docosahexaenoic acids), but not saturated fatty ac ids (myristic, palmitic, stearic acids), also reversibly activated all three types of K+ channel. 7. All three K+ channels were activated by pressure applied to the membrane (i.e. channels were stretch sensitiv e) with a half-maximal pressure of similar to 18 mmHg. The K+ channels were not blocked by 100 mu M GdCl3. 8. A decrease in intracellular pH (over the range 5.6-7.2) caused a reversible, pH-dependent increase i n channel activity whether the channel was initially activated by arac hidonic acid or stretch. 9. Glutamate, a neurotransmitter reported to generate arachidonic acid in striatal neurons, did not cause activatio n of the K+ channels when applied extracellularly in cell-attached pat ches. 10. It is suggested that the K+ channels described here belong t o a distinct family of ion channels that are activated by either fatty acids or membrane stretch. Although the physiological roles of these K+ channels are not yet known, they may be involved in cellular proces ses such as cell volume regulation and ischaemia-induced elevation of K+ loss.