Protein kinase C modulates field-evoked transmitter release from cultured rat cerebellar granule cells via a dendrotoxin-sensitive K+channel

Cousin, M. A., McLaughlin, M. and Nicholls, D. G. (1999) Protein kinase C modulates field-evoked transmitter release from cultured rat cerebellar granule cells via a dendrotoxin-sensitive K+channel. European Journal of Neuroscience, 11(1), pp. 101-109. (doi:10.1046/j.1460-9568.1999.00412.x) (PMID:9987015)

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Abstract

The role of protein kinase C (PKC) in the control of neurotransmitter release from cultured rat cerebellar granule cells was investigated. Release of preloaded [3H]‐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 Ca2+‐dependent [3H]‐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 Ca2+ 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 [3H]‐d‐aspartate release and neurite Ca2+ 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McLaughlin, Dr Mark
Authors: Cousin, M. A., McLaughlin, M., and Nicholls, D. G.
College/School:College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
Journal Name:European Journal of Neuroscience
Publisher:Wiley
ISSN:0953-816X
ISSN (Online):1460-9568

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