F. Heemskerk, L. Schrama, W. Ghijsen
Jun 1, 1991
Citations
2
Influential Citations
32
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Journal
Journal of Neurochemistry
Abstract
Abstract: Recently we have shown that 4‐aminopyridine (4‐AP), a drug known to enhance transmitter release, stimulates the phosphorylation of the protein kinase C substrate B‐50 (GAP‐43) in rat brain synaptosomes and that this effect is dependent on the presence of extracellular Ca2+. Hence, we were interested in the relationship between changes induced by 4‐AP in the intracellular free Ca2+ concentration ([Ca2+]i) and B‐50 phosphorylation in synaptosomes. 4‐AP (100 μM) elevates the [Ca2+]i (as determined with fura‐2) to approximately the same extent as depolarization with 30 mM K+ (from an initial resting level of 240 nM to ∼480 nM after treatment). However, the underlying mechanisms appear to be different: In the presence of 4‐AP, depolarization with K+ still evoked an increase in [Ca2+]i, which was additive to the elevation caused by 4‐AP. Several Ca2+ channel antagonists (CdCl2, LaCl3, and diphenylhydantoin) inhibited the increase in B‐50 phosphorylation by 4‐AP. It is interesting that the increase in [Ca2+]i and the increase in B‐50 phosphorylation by 4‐AP were attenuated by tetrodotoxin, a finding pointing to a possible involvement of Na+ channels in this action. These results suggest that 4‐AP (indirectly) stimulates both Ca2+ influx and B‐50 phosphorylation through voltage‐dependent channels by a mechanism dependent on Na+ channel activity.