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Control of Ca2+ influx by cannabinoid and metabotropic glutamate receptors in rat cerebellar cortex requires K+ channels

By H Daniel and F Crepel

Abstract

In the rodent cerebellum, both presynaptic CB1 cannabinoid receptors and presynaptic mGluR4 metabotropic glutamate receptors acutely depress excitatory synaptic transmission at parallel fibre-Purkinje cell synapses. Using rat cerebellar slices, we have analysed the effects of selective CB1 and mGluR4 agonists on the presynaptic Ca2+ influx which controls glutamate release at this synapse.Changes in presynaptic Ca2+ influx were determined with the Ca2+-sensitive dyes fluo-4FF AM or fluo-3 AM. Five stimulations delivered at 100 Hz or single stimulations of parallel fibres evoked rapid and reproducible transient increases in presynaptic fluo-4FF or fluo-3 fluorescence, respectively, which decayed to prestimulus levels within a few hundred milliseconds. Bath application of the selective CB1 agonist WIN55,212-2 (1 μm) markedly reduced the peak amplitude of these fluorescence transients. This effect was fully reversed by the selective CB1 antagonist SR141716-A (1 μm).Bath application of the selective mGluR4 agonist l-AP4 (100 μm) also caused a transient decrease in the peak amplitude of the fluorescence transients evoked by parallel fibre stimulation.Bath application of the potassium channel blocker 4-AP (1 mm) totally prevented both the WIN55,212-2- and the l-AP4-induced inhibition of peak fluorescence transients evoked by parallel fibre stimulation.The present study demonstrates that activation of CB1 and mGluR4 receptors inhibits presynaptic Ca2+ influx evoked by parallel fibre stimulation via the activation of presynaptic K+ channels, suggesting that the molecular mechanisms underlying this inhibition involve an indirect inhibition of presynaptic voltage-gated Ca2+ channels rather than their direct inhibition

Topics: Rapid Report
Publisher: Blackwell Science Inc
OAI identifier: oai:pubmedcentral.nih.gov:2279003
Provided by: PubMed Central
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