Protein kinase C as mediator of arachidonic acid-induced decrease of neuronal M current.

The M current, IM, of NG108-15 neuroblastoma x glioma hybrid cells, a non-inactivating K+ current, is decreased by arachidonic acid (5-25 microM), often after an initial transitory increase. To test the possibility that the decrease is caused by activation of protein kinase C (PKC) we used the PKC 19-31 peptide, which is an effective inhibitor of PKC. With 1 microM peptide in the pipette solution the normally observed strong reduction of IM by 1 microM phorbol 12,13-dibutyrate (PDB) was almost totally prevented, indicating that PKC is completely inhibited; also the voltage dependence of the M conductance, gM(V), was shifted to more negative membrane potentials. In the presence of 1 microM peptide the effect of 25 microM arachidonic acid on IM was significantly reduced, suggesting that the effect, or at least a large part of it, is mediated by PKC.