Acetylcholine release from synaptosomes and phenytoin action

The release of labeled acetylcholine from synaptosomes loaded with methyl-[ 3H]choline has been measured in Krebs-Ringer-Bicarbonate (KRB) media containing either 5.6 or 56 mM KCl. Experiments have been performed in media containing either 1.0 mM Ca or 0 Ca with 1 mM EGTA. Phenytoin, 2 × 10 −4 M, reduced the depolarization-dependent release of acetylcholine in media containing 1.0 mM Ca and 56 mM KCl. It also significantly increased the release of acetylcholine from undepolarized samples in 5.6 mM KCl irrespective of the Ca concentration. The drug did not affect release from synaptosomes depolarized in Ca-free media. These results confirm the hypothesis that phenytoin has a dual effect on transmitter release.