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

• Published in: Journal of neurochemistry 2000-03, Vol.74 (3), p.1026-1033
• Main Authors: CASAVANT, R. H, ZHAOHUI XU, DRYER, S. E
• Format: Article
• Language: English
• Subjects: 5,8,11,14-Eicosatetraynoic Acid - pharmacology; Animals; Arachidonic Acid - pharmacology; Biological and medical sciences; Chick Embryo; Enzyme Activation - physiology; Fatty Acids - physiology; Fatty Acids, Nonesterified - physiology; Fundamental and applied biological sciences. Psychology; Ganglia, Parasympathetic - cytology; Ganglia, Parasympathetic - drug effects; Ganglia, Parasympathetic - metabolism; Hydrogen Peroxide - pharmacology; Ion Channel Gating; Neurons - drug effects; Neurons - metabolism; Peripheral nervous system. Autonomic nervous system. Neuromuscular transmission. Ganglionic transmission. Electric organ; Phospholipases A - metabolism; Phospholipases A2; Potassium Channels - drug effects; Potassium Channels - metabolism; Vertebrates: nervous system and sense organs
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2000.0741026.x

Application of arachidonic acid evoked robust activation of large-conductance 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 pS 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+ concentration of 150 mM. Gating of these channels in cell-attached patches was potentiated by membrane stretch. Channel gating evoked by both lipids was concentration-dependent, with detectable activation apparent at 4 microM in the majority of patches and maximal activation occurring between 32 and 64 microM. Gating was relatively voltage-independent. Large-conductance K+ channels were also activated in inside-out patches by the monounsaturated fatty acid 11-cis-eicosenoic acid but not by the fully saturated fatty acid arachidic acid. Application of 100 microM H2O2, an agent that activates cytosolic phospholipase A2, also caused activation of large-conductance K+ channels in intact neurons. The stimulatory effects of H2O2 were blocked by pretreatment with 20 microM 4-bromophenacyl bromide, an irreversible inhibitor of phospholipase A2. Therefore, mobilization of endogenous fatty acids can cause activation of large-conductance K+ channels in autonomic neurons.