Implication of protein kinase C in mechanisms of potassium-induced long-term potentiation in rat hippocampal slices.

The involvement of Ca2+/phospholipid-dependent (alpha, beta, gamma, PKCs) and Ca(2+)-independent PKC (epsilon and zeta isoforms) in mechanisms of long-term potentiation was investigated in CA1 hippocampal slices, using a brief high potassium pulse (50 mM, 40 s) to induce long-term potentiation (K+/LTP). The K+ pulse induced first, in 15 s a translocation of PKC activity to the membrane. This was rapidly followed, from 1 to 60 min after the pulse, by a selective activation of PKC in the cytosol. This activation, which could be blocked by the NMDA (N-methyl-D-aspartate) receptor antagonist 2-amino-5-phosphonovalerate (APV), was associated with a significant increase n immunoreactivity for gamma PKC in he cytosol, and also to a less degree for beta PKC. In contrast, application of the phorbol ester PMA (phorbol 12-mirystate 13 acetate) to other slices induced a rapid and persistent translocation to the membrane of alpha, beta, epsilon and zeta PKCs. A major role for the activation role for the activation of cytosolic gamma PKC in the maintenance of LTP is discussed.