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Modulation of neuronal phospholipase D activity under depolarizing conditions
Author(s) -
Waring Mark,
Drappatz Jan,
Weichel Oksana,
Seimetz Petra,
Sarri Elisabet,
Böckmann Ira,
Kempter Ulrike,
Valeva Angela,
Klein Jochen
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01669-5
Subject(s) - depolarization , ouabain , chemistry , synaptosome , biophysics , calcium , veratridine , phospholipase c , phospholipase d , biochemistry , endocytosis , biology , sodium , sodium channel , signal transduction , in vitro , receptor , organic chemistry
Neuronal phospholipase D (PLD) activity was hypothesized to be involved in vesicle trafficking and endocytosis and, possibly, transmitter release. We here report that prolonged depolarization of rat hippocampal slices by potassium chloride (KCl) or 4‐aminopyridine inhibited PLD activity. Similarly, PLD activity in rat cortical synaptosomes was significantly inhibited by depolarizing agents including veratridine and ouabain. Inhibition of calcium/calmodulin kinase II (CaMKII) which positively modulates synaptosomal PLD activity [Sarri et al. (1998) FEBS Lett. 440, 287–290] by KN‐62 caused a further reduction of PLD activity in depolarized synaptosomes. Depolarization‐induced inhibition of PLD activity was apparently not due to transmitter release or activation of other kinases. We observed, however, that KCl‐induced depolarization caused an increase of inositol phosphates and a reduction of the synaptosomal pool of phosphatidylinositol‐4,5‐bisphosphate (PIP 2 ). Moreover, in synaptosomes permeabilized with Staphylococcus aureus α‐toxin, PLD activation induced by calcium was abolished by neomycin, a PIP 2 chelator. We conclude that depolarizing conditions cause an inhibition of neuronal PLD activity which is likely due to breakdown of PIP 2 , a required cofactor for PLD activity. Our findings suggest that neuronal PLD activity is regulated by synaptic activity.