12-Lipoxygenase overexpression in rodent NG108-15 cells enhances membrane excitability by inhibiting M-type K+ channels.
1. 12-Lipoxygenase produces 12-hydroperoxy acid from arachidonic acid released from membrane phospholipids. To elucidate the role of the enzyme in neuronal functions, mouse neuroblastoma x rat glioma hybrid NG108-15 cells were permanently transfected with the cDNA for human 12-lipoxygenase. 2. The number of action potentials evoked by depolarizing current steps in a current-clamp mode was strikingly increased in 12-lipoxygenase-expressing NG108-15 cells as compared with the wild-type cells which hardly had the enzyme activity. 3. In the transformed cells, the M-type voltage-dependent K+ current was significantly reduced with little or no change in other ion channel currents. 4. Treatment of the transformed cells with a 12-lipoxygenase inhibitor recovered the action potential frequency and the M-current amplitude to the control level. 5. These results indicate that 12-lipoxygenase and/or its metabolites target K+ channels and upregulate the membrane excitability, and thereby modulate neuronal signalling.
Takahashi
Y
Y
Department of Pharmacology, Kanazawa University School of Medicine, Japan. takahash@med.kanazawa-u.ac.jp
Kawajiri
H
H
Yoshimoto
T
T
Hoshi
N
N
Higashida
H
H
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000096:biosynthesis* / Q000235:genetics; D016718:Arachidonic Acid / Q000378:metabolism; D001932:Brain Neoplasms / Q000503:physiopathology; D004594:Electrophysiology; D005910:Glioma / Q000503:physiopathology; D006822:Hybrid Cells; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D009447:Neuroblastoma / Q000503:physiopathology; D009474:Neurons / Q000502:physiology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D051381:Rats; D014162:Transfection; D014407:Tumor Cells, Cultured
D026902:Potassium Channel Blockers; D016718:Arachidonic Acid; D001092:Arachidonate 12-Lipoxygenase