Direct modulation of Aplysia S-K+ channels by a 12-lipoxygenase metabolite of arachidonic acid.
Lipoxygenase metabolites of arachidonic acid have recently been shown to modulate the activity of ion channels in nerve and muscle cells. The mechanism of action of these metabolites is, however, unknown. In sensory neurons of Aplysia, the S-K- channel is under the dual modulatory control of 5-hydroxytryptamine (5-HT), which decreases the number of active S channels through cyclic AMP-dependent phosphorylation, and the neuropeptide FMRFamide, which increases the probability of S-channel opening through the 12-lipoxygenase metabolite 12-hydroperoxyeicosatetraenoic acid (12-HPETE). Here we report that the increase in the probability of S-channel opening with FMRFamide is mimicked by application of 12-HPETE to cell-free membrane patches that lack ATP and GTP. Thus, 12-HPETE can act directly to modulate S-channel activity, independently of protein phosphorylation or dephosphorylation, G-protein activation or cyclic nucleotides.
Buttner
N
N
Department of Pharmacology, Howard Hughes Medical Institute, Columbia University, New York, New York 10032.
Siegelbaum
S A
SA
Volterra
A
A
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D001048:Aplysia; D001092:Arachidonate 12-Lipoxygenase / Q000502:physiology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D002474:Cell-Free System; D019835:FMRFamide; D019204:GTP-Binding Proteins / Q000502:physiology; D006160:Guanosine Triphosphate / Q000502:physiology; D066298:In Vitro Techniques; D015289:Leukotrienes / Q000502:physiology; D009479:Neuropeptides / Q000502:physiology; D009712:Nucleotides, Cyclic / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*
D001095:Arachidonic Acids; D015289:Leukotrienes; D009479:Neuropeptides; D009712:Nucleotides, Cyclic; D015221:Potassium Channels; D016718:Arachidonic Acid; D012701:Serotonin; D019835:FMRFamide; C021201:12-HPETE; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D001092:Arachidonate 12-Lipoxygenase; D019204:GTP-Binding Proteins