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-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.
Casavant
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Department of Biology and Biochemistry, University of Houston, Texas 77205-5513, USA.
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Dryer
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D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D002642:Chick Embryo; D004789:Enzyme Activation / Q000502:physiology; D005227:Fatty Acids / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000502:physiology; D005726:Ganglia, Parasympathetic / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015640:Ion Channel Gating; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*
D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D015221:Potassium Channels; D015117:5,8,11,14-Eicosatetraynoic Acid; D016718:Arachidonic Acid; D006861:Hydrogen Peroxide; D010741:Phospholipases A; D054467:Phospholipases A2