Oleic acid enhances ACh receptor currents by activation of Ca2+/calmodulin-dependent protein kinase II.
Oleic acid, a cis-unsaturated free fatty acid, is proposed to be involved in the protein kinase C (PKC) activation pathway. Its biological actions, however, have not been well-characterized. We examined the effects of oleic acid on acetylcholine (ACh)-gated channel currents using Torpedo nicotinic ACh receptors expressed in Xenopus oocytes. Oleic acid (10 microM) enhanced the currents, reaching a maximum (140%) 20 min after treatment, while no enhancement was observed in Ca(2+)-free extracellular solution. The current potentiation by oleic acid was not inhibited by PKC inhibitors such as PKCI or GF109203X. Furthermore, oleic acid potentiated the currents in mutant ACh receptors lacking potential PKC phosphorylation sites. In contrast, the potentiation was fully inhibited by a CaMKII inhibitor, KN-62. These results strongly suggest that oleic acid potentiates ACh receptor currents by activation of calmodulin-dependent protein kinase II (CaMKII), independent of the PKC pathway.
Nishizaki
T
T
Department of Physiology, Kobe University School of Medicine, Japan.
Ikeuchi
Y
Y
Matsuoka
T
T
Sumikawa
K
K
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007211:Indoles / Q000494:pharmacology; D007700:Kinetics; D046911:Macromolecular Substances; D008301:Maleimides / Q000494:pharmacology; D016297:Mutagenesis, Site-Directed; D019301:Oleic Acid / Q000494:pharmacology*; D009865:Oocytes / Q000502:physiology*; D017354:Point Mutation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011978:Receptors, Nicotinic / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D012694:Serine; D014101:Torpedo; D014982:Xenopus laevis
D004791:Enzyme Inhibitors; D007211:Indoles; D046911:Macromolecular Substances; D008301:Maleimides; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins; D019301:Oleic Acid; D012694:Serine; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C070515:bisindolylmaleimide I; D000109:Acetylcholine