Protein kinase C inhibitors affect induction of long-lasting potentiation in the somatosensory cortex.

The effects of protein kinase C (PKC) inhibitors on the induction of long lasting potentiation (LLP) of field potentials in the feline somatosensory cortex were studied. LLP was induced by high frequency stimulation (HFS, 200 Hz) of the ventral posterolateral thalamic nucleus. First, the effects of a protein kinase inhibitor, H-7, and a specific PKC catalytic domain inhibitor, chelerythrine, on the LLP in the secondary somatosensory cortex (SII) were investigated. Intracortical microinjections of H-7 and chelerythrine at 30 min before HFS inhibited induction of LLP in SII, while an injection of chelerythrine at 60 min after LLP induction had no effect on the potentiation. Second, changes in PKC activity in the presence of calcium and phosphatidylserine were investigated in SII after induction of LLP. Triton-soluble membrane fractional PKC activity had increased to 350% of the control value with low frequency test stimulation (0.1 Hz) by five min after HFS. In contrast, PKC activities of cytosolic fractions decreased to 25.6% of the control value. At 60 min after HFS, the PKC activity level returned to the control value, despite persistent potentiation in all cases. PKC activation is considered to be one of the factors required for induction of LLP but not for maintenance in SII.