The slow EPSC (sEPSC) of cerebellar parallel fiber 3 Purkinje neuron synapses is mediated by metabotropic glutamate receptor type 1 (mGluR1) activation of nonselective cation channels. Here, the channel properties were studied with uniform calibrated photorelease of L-glutamate with ionotropic receptors blocked, allowing isolation of postsynaptic processes, or with parallel fiber stimulation or mGluR1 agonist application. Evoked current and fluorescence from Ca 2ϩ indicators were recorded.

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... analysis of the mGluR1 current gave a single-channel conductance of 0.6 pS and showed low open probability at maximal mGluR1 activation. Similar small single-channel conductances were obtained with the mGluR1 agonist (S)-dihydroxyphenylglycine, with parallel fiber or climbing fiber stimulation. The mGluR1 current fluctuations were unaffected by potassium channel blockers. Photoreleased L-glutamate triggered a Ca 2ϩ concentration increase in the distal dendrites with a time course similar to that of the mGluR1 current. The proximal dendritic and somatic Ca 2ϩ changes were delayed with respect to the current. Ca 2ϩ channel blockers and the phospholipase C␤ inhibitor 1-[6-[((17␤)-3methoxyestra-1,3,5[10]-trien-17-yl)amino]hexyl]-1H -pyrrole-2,5-dione, which inhibits mGluR1-activated intracellular Ca 2ϩ release, did not prevent the dendritic Ca 2ϩ concentration increase. Polyamine naphthylacetyl spermine and cationic adamantanes that block the pore of the channel were used to vary the mGluR1 current over a wide range in each cell but still at maximal mGluR1 activation. The Ca 2ϩ influx was inhibited in parallel with the current. The results show that the mGluR1-activated current and the sEPSC are attributable to small-conductance, low-open probability Ca 2ϩ -permeable cation channels that will mediate spine-specific Ca 2ϩ influx during the parallel fiber sEPSP.