Activation of protein kinase C by 4-aminopyridine dependent on Na+ channel activity in rat hippocampal slices.
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.
Heemskerk
F M
FM
Division of Molecular Neurobiology, Rudolf Magnus Institute, Utrecht, The Netherlands.
Schrama
L H
LH
Gispen
W H
WH
D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008666:Metalloendopeptidases / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D015222:Sodium Channels; D013779:Tetrodotoxin; D015761:4-Aminopyridine; D011494:Protein Kinases; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus