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Roscovitine differentially facilitates cerebellar glutamatergic and GABAergic neurotransmission by enhancing Ca v 2.1 channel‐mediated multivesicular release
Author(s) -
Satake Shin’Ichiro,
Konishi Shiro
Publication year - 2020
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 - 10.1111/ejn.14771
Subject(s) - postsynaptic current , excitatory postsynaptic potential , glutamatergic , chemistry , neuroscience , neurotransmission , inhibitory postsynaptic potential , exocytosis , biophysics , postsynaptic potential , synaptic vesicle , glutamate receptor , biology , vesicle , biochemistry , secretion , receptor , membrane
Synaptic vesicle exocytosis is triggered by Ca 2+ influx through several subtypes of voltage‐gated calcium channels in the presynaptic terminal. We previously reported that paired‐pulse stimulation at brief intervals increases Ca v 2.1 ( P / Q ‐type) channel‐mediated multivesicular release (MVR) at glutamatergic synapses between granule cells (GCs) and molecular layer interneurons (MLIs) in rat cerebellar slices. However, it has yet to be determined how Ca v 2 channel subtypes take part in MVR in single axon terminal. This study therefore aimed at examining the effects of roscovitine on different types of cerebellar synapses that make contacts with Purkinje cells (PCs), because this compound has been shown to enhance Ca v 2.1 channel‐mediated MVR at GC‐MLI synapses. Bath application of roscovitine profoundly increased the amplitude of excitatory postsynaptic currents (EPSCs) at GC‐PC synapses by a presynaptic mechanism as previously observed at GC‐MLI synapses, whereas it caused a marginal effect on climbing fiber‐mediated EPSCs in PCs. At MLI‐PC synapses, roscovitine increased both the amplitude and decay time of inhibitory postsynaptic currents (IPSCs) by enhancing multivesicular GABA release. When extracellular Ca 2+ concentration ([Ca 2+ ] e ) decreased, roscovitine became less effective in increasing GC‐PC EPSCs. By contrast, roscovitine was able to augment MLI‐PC IPSCs in the low [Ca 2+ ] e . The Ca v 2.1 channel blocker ω‐agatoxin IVA suppressed the roscovitine‐induced facilitatory actions on both GC‐PC EPSCs and MLI‐PC IPSCs. These results demonstrate that roscovitine enhances MVR at the GC‐PC excitatory synapses in a manner dependent on the driving force of Ca v 2.1 channel‐mediated Ca 2+ influx into the nerve terminal, while it also facilitates MLI‐PC inhibitory transmission via Ca 2+ ‐insensitive mechanisms.