PROTEIN-KINASE-C AS MEDIATOR OF ARACHIDONIC ACID-INDUCED DECREASE OF NEURONAL M-CURRENT

The M current, I-M, of NG108-15 neuroblastoma X glioma hybrid cells, a non-inactivating K+ current, is decreased by arachidonic acid (5-25 m u M), often after an initial transitory increase. To test the possibil ity 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 PK C. With 1 mu M peptide in the pipette solution the normally observed s trong reduction of I-M by 1 mu M phorbol 12,13-dibutyrate (PDB) was al most totally prevented, indicating that PKC is completely inhibited; a lso the voltage dependence of the M conductance, g(M)(V), was shifted to more negative membrane potentials. In the presence of 1 mu M peptid e the effect of 25 mu M arachidonic acid on I-M was significantly redu ced, suggesting that the effect, or at least a large part of it, is me diated by PKC.