Ca2+ ion permeability and single-channel properties of the metabotropic slow EPSC of rat Purkinje neurons

J Neurosci. 2004 Apr 7;24(14):3563-73. doi: 10.1523/JNEUROSCI.5374-03.2004.


The slow EPSC (sEPSC) of cerebellar parallel fiber --> 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(2+) indicators were recorded. Noise 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(2+) concentration increase in the distal dendrites with a time course similar to that of the mGluR1 current. The proximal dendritic and somatic Ca(2+) changes were delayed with respect to the current. Ca(2+) channel blockers and the phospholipase Cdelta inhibitor 1-[6-[((17delta)-3-methoxyestra-1,3,5[10]-trien-17-yl)amino]hexyl]-1H-pyrrole-2,5-dione, which inhibits mGluR1-activated intracellular Ca(2+) release, did not prevent the dendritic Ca(2+) 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(2+) 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(2+)-permeable cation channels that will mediate spine-specific Ca(2+) influx during the parallel fiber sEPSP.

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism
  • Cell Membrane Permeability / drug effects
  • Cell Membrane Permeability / physiology
  • Cerebellum / cytology
  • Cerebellum / metabolism
  • Cerebellum / physiology
  • Electric Stimulation
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology*
  • Glutamates / metabolism
  • Glutamates / pharmacology
  • In Vitro Techniques
  • Indoles / metabolism
  • Indoles / pharmacology
  • Ion Channels / drug effects
  • Ion Channels / metabolism
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Photochemistry
  • Purkinje Cells / drug effects
  • Purkinje Cells / metabolism*
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / agonists
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / metabolism*


  • 2-amino-5-(5-((methoxycarbonyl)methyl)-7-nitroindol-1-yl)-5-oxopentanoic acid
  • 4-methoxy-7-nitroindolinyl-glutamate
  • Calcium Channel Blockers
  • Calcium Channels
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Glutamates
  • Indoles
  • Ion Channels
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor type 1
  • Calcium