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Protein kinase C modulates field‐evoked transmitter release from cultured rat cerebellar granule cells via a dendrotoxin‐sensitive K + channel
Author(s) -
Cousin Michael A.,
McLaughlin Mark,
Nicholls David G.
Publication year - 1999
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.1999.00412.x
Subject(s) - protein kinase c , staurosporine , exocytosis , depolarization , synaptic vesicle , biophysics , chemistry , cerebellum , microbiology and biotechnology , biology , vesicle , neuroscience , biochemistry , phosphorylation , membrane
The role of protein kinase C (PKC) in the control of neurotransmitter release from cultured rat cerebellar granule cells was investigated. Release of preloaded [ 3 H]‐ d ‐aspartate which is incorporated into synaptic vesicles in this preparation was evoked by electrical field stimulation or elevated KCl. PKC activation by phorbol esters resulted in a large facilitation of field‐evoked Ca 2+ ‐dependent [ 3 H]‐ d ‐aspartate release and a lesser enhancement of KCl‐stimulated release. Inhibition of PKC by Ro 31‐8220 or staurosporine virtually abolished field‐evoked release but had no effect on KCl‐evoked release. Field‐evoked, but not KCl‐evoked, synaptic vesicle exocytosis monitored by the fluorescent vesicle probe FM2‐10 was inhibited by staurosporine. PKC was not directly modulating neurite Ca 2+ channels coupled to release, as Ro 31‐8220 did not inhibit these channels. Activation or inhibition of PKC modulated field‐evoked plasma membrane depolarization, but had no effect on KCl‐evoked depolarization, consistent with a regulation of Na + or K + channels activated by field stimulation. No modulation of field‐evoked neurite Na + influx was seen using phorbol esters. Phorbol ester‐induced facilitation of field‐evoked [ 3 H]‐ d ‐aspartate release and neurite Ca 2+ entry was non‐additive with that produced by the specific K + channel antagonist dendrotoxin‐1, suggesting that PKC modulates transmitter release from field‐stimulated cerebellar granule cells by inhibiting a dendrotoxin‐1‐sensitive K + channel.