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4‐Aminopyridine Stimulates B‐50 (GAP43) Phosphorylation and [ 3 H]Noradrenaline Release in Rat Hippocampal Slices
Author(s) -
Heemskerk F. M. J.,
Schrama L. H.,
Gianotti C.,
Spierenburg H.,
Versteeg D. H. G.,
De Graan P. N. E.,
Gispen W. H.
Publication year - 1990
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1990.tb02331.x
Subject(s) - phosphorylation , convulsant , 4 aminopyridine , hippocampal formation , chemistry , medicine , endocrinology , biophysics , biochemistry , biology , receptor , potassium channel
In situ phosphorylation of the presynaptic protein kinase C substrate B‐50 was investigated in rat hippocampal slices incubated with the convulsant drug 4‐aminopyridine (4‐AP). Phosphorylation of B‐50 was significantly enhanced 1 min after the addition of 4‐AP (100 μM ). This increase by 4‐AP was concentration dependent (estimated EC 50 30–50). Concomitant with the changes in B‐50 phosphorylation, 4‐AP also dose‐dependently stimulated [ 3 H]noradrenaline ([ 3 H]NA) release from the slices. 4‐AP stimulated [ 3 H]NA release within 5 min to seven times the control level. The B‐50 phosphorylation induced by 4‐AP remained elevated after removal of the convulsant, this in contrast to B‐50 phosphorylation induced by depolarization with K + . A similar persistent increase was observed for [ 3 H]NA release after a 5‐min incubation period with 4‐AP. These results give more insight into the molecular mechanisms underlying 4‐AP‐induced epileptogenesis and provide further evidence for the correlation between B‐50 phosphorylation and neurotransmitter release in the hippocampal slice.