000160715 001__ 160715
000160715 005__ 20180317092717.0
000160715 0247_ $$2doi$$a10.1523/JNEUROSCI.0550-08.2008
000160715 022__ $$a0270-6474
000160715 02470 $$2ISI$$a000258423400014
000160715 037__ $$aARTICLE
000160715 245__ $$aPhorbol esters modulate spontaneous and Ca2+-evoked transmitter release via acting on both munc13 and protein kinase C
000160715 269__ $$a2008
000160715 260__ $$bSociety for Neuroscience$$c2008
000160715 336__ $$aJournal Articles
000160715 520__ $$aDiacylglycerol (DAG) and phorbol esters strongly potentiate transmitter release at synapses by activating protein kinase C (PKC) and members of the Munc13 family of presynaptic vesicle priming proteins. This PKC/Munc13 pathway has emerged as a crucial regulator of release probability during various forms of activity-dependent enhancement of release. Here, we investigated the relative roles of PKC and Munc13-1 in the phorbol ester potentiation of evoked and spontaneous transmitter release at the calyx of Held synapse. The phorbol ester phorbol 12,13-dibutyrate (1 mu M) potentiated the frequency of miniature EPSCs, and the amplitudes of evoked EPSCs with a similar time course. Preincubating slices with the PKC blocker Ro31-82200 reduced the potentiation, mainly by affecting a late phase of the phorbol ester potentiation. The Ro31-8220-insensitive potentiation was most likely mediated by Munc13-1, because in organotypic slices of Munc13-1H567K knock-in mice, in which DAG binding to Munc13-1 is abolished, the potentiation of spontaneous release by phorbol ester was strongly suppressed. Using direct presynaptic depolarizations in paired recordings, we show that the phorbol ester potentiation does not go along with an increase in the number of readily releasable vesicles, despite an increase in the cumulative EPSC amplitude during 100 Hz stimulation trains. Our data indicate that activation of Munc13 and PKC both contribute to an enhancement of the fusion probability of readily releasable vesicles. Thus, docked and readily releasable vesicles are a substrate for modulation via intracellular second-messenger pathways that act via Munc13 and PKC.
000160715 6531_ $$asynapse
000160715 6531_ $$areadily releasable pool
000160715 6531_ $$arelease probability
000160715 6531_ $$asecond messenger
000160715 6531_ $$adiacylglycerol
000160715 6531_ $$aorganotypic culture
000160715 6531_ $$aSynaptic Vesicle Fusion
000160715 6531_ $$aAuditory Brain-Stem
000160715 6531_ $$aNeurotransmitter Release
000160715 6531_ $$aPostsynaptic Currents
000160715 6531_ $$aChromaffin Cells
000160715 6531_ $$aDetermines Fast
000160715 6531_ $$aCa2+ Sensor
000160715 6531_ $$aPool
000160715 6531_ $$aCalyx
000160715 6531_ $$aPhosphorylation
000160715 700__ $$aLou, Xuelin
000160715 700__ $$aKorogod, Natalya
000160715 700__ $$aBrose, Nils
000160715 700__ $$0244726$$aSchneggenburger, Ralf$$g169973
000160715 773__ $$j28$$k33$$q8257-8267$$tJournal Of Neuroscience
000160715 8564_ $$s635600$$uhttps://infoscience.epfl.ch/record/160715/files/8257.pdf$$yPublisher's version$$zn/a
000160715 909CO $$ooai:infoscience.tind.io:160715$$particle$$pSV
000160715 909C0 $$0252339$$pLSYM$$xU11233
000160715 917Z8 $$xWOS-2010-11-30
000160715 917Z8 $$x182396
000160715 937__ $$aEPFL-ARTICLE-160715
000160715 973__ $$aEPFL$$rREVIEWED$$sPUBLISHED
000160715 980__ $$aARTICLE