Fatty acid-activated K+ channels in autonomic neurons: Activation by an endogenous source of free fatty acids

Application of arachidonic acid evoked robust activation of large-conductan ce K+ channels in cell-attached and excised inside-out patches from acutely isolated chick ciliary ganglion neurons. A similar effect was produced by 5,8,11,14-eicosatetraynoic acid, a nonmetabolizable analogue of arachidonic acid. The unitary conductance of fatty acid-activated channels was 35-40 p S at +20 mV with physiological gradients of K+ and 165 pS at +20 mV with an extracellular K+ concentration of 37.5 mM and an intracellular K+ concentr ation of 150 mM. Gating of these channels in cell-attached patches was pote ntiated by membrane stretch. Channel gating evoked by both lipids was conce ntration-dependent, with detectable activation apparent at 4 mu M in the ma jority of patches and maximal activation occurring between 32 and 64 mu M. Gating was relatively voltage-independent. Large-conductance K+ channels we re also activated in inside-out patches by the monounsaturated fatty acid 1 1-cis-eicosenoic acid but not by the fully saturated fatty acid arachidic a cid. Application of 100 mu M H2O2, an agent that activates cytosolic phosph olipase A(2), also caused activation of large-conductance K+ channels in in tact neurons. The stimulatory effects of H2O2 were blocked by pretreatment with 20 mu M 4-bromophenacyl bromide, an irreversible inhibitor of phosphol ipase A(2). Therefore, mobilization of endogenous fatty acids can cause act ivation of large-conductance K+ channels in autonomic neurons.