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The convulsant drug 4-aminopyridine (4-AP) stimulates the phosphorylation of the neuron-specific presynaptic protein B-50 in hippocampal slices. This effect could be attenuated by the protein kinase C (PKC) inhibitor staurosporine. Moreover, the endogenous phosphorylation of B-50 was found to be restricted to the 15 kDa Staphylococcus aureus protease fragment of B-50, known to contain the PKC acceptor site. The effect of 4-AP on B-50 phosphorylation was sensitive to the Na+ channel blocker tetrodotoxin. These results indicate that 4-AP stimulates PKC activity in hippocampal slices by a mechanism dependent on Na+ channel activity.
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