The slow EPSP in Purkinje neurones (PN) due to activation of mGluR1 receptors at parallel fibre synapses is mediated by a non-selective cation channel (Canepari et al. 2001). mGluR1 sEPSCs were activated by photorelease of L-glutamate in 20-day rat cerebellar slices in 0.1 mM AMPAR antagonist NBQX. Biophysical and pharmacological characteristics of the sEPSC channel were compared with those of recombinant ‘lurcher’ GluRδ₂ channels. In PN, noise analysis gave a single channel conductance of 0.21 pS and low open probability at the peak sEPSC. Moreover, Ca²⁺ imaging with Ca²⁺ channels and PLC blocked showed the sEPSC channel is permeable to Ca²⁺. The PN mGluR1 conductance was not affected by divalent cations that block cyclic nucleotide-gated channels, nor the I_H blocker ZD1722, nor the purinergic blocker PPADS, nor the TRP channel blocker Gd³⁺ (0.01 mM internally, 0.1 mM externally), nor TrKB blocker K252a. It was blocked by the pore-blockers naphthylacetyl spermine (0.1 mM) and adamantane derivatives IEM 1460 (Magazanik et al. 1997) or rimantadine (0.1Ð1 mM) in a use-dependent manner. The NMDA blocker MK801 (0.1 mM) and local anaesthetic nAChR blocker QX314 (0.2 mM) had no effect. Linolenic acid (0.02 mM), which blocks kainate channels, blocked the mGluR1 response. This suggests that an unedited AMPA-kainate glutamate channel underlies the sEPSP.

GluRδ₂ are present at high density in PN spines at parallel fibre synapses. For comparison of pore properties with the PN mGluR1 channel, the constitutively active Ca²⁺-permeable ‘lurcher’ mutation of GluRδ₂ was tested in HEK cells (Wollmuth et al. 2000). The single channel conductance was 0.3 pS and the open probability low, < 10 %, at 2 mM Ca²⁺, similar to the PN channel. The results with pore blockers were also similar to the PN sEPSC; naphthylacetylspermine and the adamantane derivatives showed open channel block at 0.1Ð0.5 mM, linolenic acid blocked at 0.02 mM, and MK801, QX314 and mGluR1 blocker CPCCoEt (0.02 mM) were ineffective in GluRδ₂.

The similar biophysical and pharmacological properties, and the ineffectiveness of blockers of other candidate channels present in Purkinje neurones, strongly supports the proposal that the ion channel underlying the sEPSP in cerebellar Purkinje neurones is the Ca²⁺-permeable GluRδ₂.

We thank J. Corrie and G. Papageorgiou for NI-caged glutamate.

All procedures accord with current local guidelines.