The conductance underlying the parallel fibre slow EPSP in rat cerebellar Purkinje neurones studied with photolytic release of L‐glutamate

Publisher Website
Google Scholar
Abstract
1. Tetanic stimulation of parallel fibres (PFs) produces a slow EPSP (sEPSP) or slow EPSC (sEPSC) in Purkinje neurones (PNs), mediated by type 1 metabotropic glutamate receptors (mGluR1). The conductance change underlying the sEPSP was investigated with rapid photolytic release of L-glutamate from nitroindolinyl (NI)-caged glutamate with ionotropic glutamate receptors blocked, and showed a slow mGluR1-activated cation channel. 2. In cerebellar slices rapid photolytic release (t (1/2) < 0.7 ms) of 7--70 microM L-glutamate on PNs voltage clamped at -65 mV activated first a transient inward current, peaking in 8 ms, followed by a slow inward current with time course similar to the PF sEPSP, peaking at -1 nA in 700 ms. 3. The initial current was inhibited by 300 microM threo-hydroxyaspartate (THA) and did not reverse as the potential was made positive up to +50 mV, suggesting activation of electrogenic glutamate uptake. 4. The slow current was inhibited reversibly by 1 mM (R,S)-MCPG or the non-competitive mGluR1 antagonist CPCCOEt (20 microM), indicating activation of metabotropic type 1 glutamate receptors. The mGluR current was associated with increases of input conductance and membrane current noise, and reversed close to 0 mV, indicating activation of channels permeant to Na(+) and K(+). 5. The sEPSC was not blocked by Cd(2+), Co(2+), Mg(2+) or Gd(3+) ions, by the inhibitor of hyperpolarisation-activated current (I(H)) ZD7288, or by the purinoceptor inhibitor PPADS. Activation was not affected by inhibitors of phospholipase C (PLC) or protein kinase C (PKC), nor mimicked by photorelease of InsP(3) or Ca(2+). The results show that mGluR1 in PNs produces a slow activation of cation-permeable ion channels which is not mediated by PLC activation, Ca(2+) release from stores, or via the activation of PKC.