Premium
Control of Ca 2+ influx by cannabinoid and metabotropic glutamate receptors in rat cerebellar cortex requires K + channels
Author(s) -
Daniel H.,
Crepel F.
Publication year - 2001
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2001.00793.x
Subject(s) - metabotropic glutamate receptor , neuroscience , metabotropic receptor , cerebellar cortex , chemistry , glutamate receptor , cannabinoid receptor , metabotropic glutamate receptor 7 , long term depression , metabotropic glutamate receptor 5 , metabotropic glutamate receptor 6 , metabotropic glutamate receptor 1 , metabotropic glutamate receptor 8 , receptor , cerebellum , biology , biochemistry , agonist , ampa receptor
1 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 Ca 2+ influx which controls glutamate release at this synapse. 2 Changes in presynaptic Ca 2+ influx were determined with the Ca 2+ ‐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 μ m ) markedly reduced the peak amplitude of these fluorescence transients. This effect was fully reversed by the selective CB1 antagonist SR141716‐A (1 μ m ). 3 Bath application of the selective mGluR4 agonist l ‐AP4 (100 μ m ) also caused a transient decrease in the peak amplitude of the fluorescence transients evoked by parallel fibre stimulation. 4 Bath application of the potassium channel blocker 4‐AP (1 m m ) totally prevented both the WIN55,212‐2‐ and the l ‐AP4‐induced inhibition of peak fluorescence transients evoked by parallel fibre stimulation. 5 The present study demonstrates that activation of CB1 and mGluR4 receptors inhibits presynaptic Ca 2+ 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 Ca 2+ channels rather than their direct inhibition.