Evidence that protein kinase M does not maintain long-term potentiation.

We have shown that the induction but not maintenance of long-term potentiation (LTP) in the Schaffer collateral-CA1 synaptic zone of the rat hippocampus is blocked by the extracellular application of the protein kinase inhibitor staurosporine. This compound was also found to block the induction of LTP in the perforant path-granule cell synaptic zone of the intact hippocampus. We have determined that staurosporine is membrane-permeable and can be detected inside cells by fluorescence microscopy. When cultured fetal hippocampal neurons were treated with staurosporine, fluorescence was observed throughout the cytoplasm and in neurites. Other cell types gave similar results. It has been proposed that constitutively active cytosolic protein kinase M or other protein kinases maintain long-term potentiation. Since staurosporine has access to the cytosol and inhibits protein kinase M in vitro, our results suggest that this enzyme is not responsible for the maintenance of LTP. This conclusion may extend to other protein kinases as well, since staurosporine has been shown to inhibit a variety of these enzymes.