12-lipoxygenase overexpression in rodent NG108-15 cells enhances membrane excitability by inhibiting M-type K+ channels

1. 12-Lipoxygenae produces 12-hydroperoxy acid from arachidonic acid releas ed from membrane phospholipids. To elucidate the role of the enzyme in neur onal 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-damp mode was strikingly increased in 12-lipoxygenase-expressing NG108-15 cells as compared with the wild-type cells which hardly had the en zyme activity. 3. In the transformed cells, the M-type voltage-dependent K+ current was si gnificantly reduced with little or no change in other ion channel currents. 4. Treatment of the transformed cells with a 12-lipoxygenase inhibitor reco vered the action potential frequency and the M-current amplitude to the con trol level. 5. These results indicate that 12-lipoxygenase and/or its metabolites targe t K+ channels and upregulate the membrane excitability, and thereby modulat e neuronal signalling.