Activity-dependent change in AMPA receptor properties in cerebellar stellate cells.
High-frequency synaptic stimulation is thought to cause a rapid and lasting change in the expression of GluR2 subunit-containing AMPA receptors (AMPARs) at synapses in cerebellar stellate cells. We examined whether spontaneous synaptic activity affects the expression of GluR2-containing synaptic AMPARs and whether the change in AMPAR subtypes alters their Ca(2+) permeability and kinetic properties. We used intracellular spermine, which blocks GluR2-lacking receptors at depolarized potentials, to distinguish the presence of GluR2. In most cells, the spontaneous EPSC frequency was low, and evoked EPSCs displayed inwardly rectifying I-V relationships, indicative of the presence of GluR2-lacking AMPARs. However, in cells that displayed a higher rate of spontaneous synaptic activity, EPSCs gave linear I-V plots, suggesting the presence of GluR2-containingAMPARs. This is consistent with the idea that spontaneous synaptic activity increased the expression of GluR2-containing AMPARs at synapses. The Ca(2+) permeability of AMPARs that gave inwardly rectifying currents in outside-out patches from TTX-treated cells was six times higher than in control cells that gave linear or outwardly rectifying I-V plots. However, increased spontaneous synaptic activity did not significantly alter the EPSC decay time. Furthermore, the decay time course ofEPSCs mediated by GluR2-containing receptors was not different from that mediated by a mixed population of receptors at the same synapse. Our results suggest that the level of spontaneous synaptic activity can determine the subunit composition of postsynaptic receptors at this synapse. The activity-induced expression of GluR2-containing receptors significantly reduced the Ca(2+) permeability of AMPARs in stellate cells but did not slow the decay time course of synaptic currents.
Liu
Siqiong June
SJ
Department of Pharmacology, University College London, London WC1E 6BT, United Kingdom. s.liu@ucl.ac.uk
Cull-Candy
Stuart G
SG
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001581:Benzothiadiazines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004232:Diuretics; D004558:Electric Stimulation / Q000379:methods; D004594:Electrophysiology; D018846:Excitatory Amino Acids / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000145:classification / Q000378:metabolism*; D049993:Sodium Chloride Symporter Inhibitors / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
D001581:Benzothiadiazines; D004232:Diuretics; D018846:Excitatory Amino Acids; D018091:Receptors, AMPA; D049993:Sodium Chloride Symporter Inhibitors; D013096:Spermine; D018698:Glutamic Acid; D013779:Tetrodotoxin; C104722:glutamate receptor ionotropic, AMPA 2; C004639:cyclothiazide; D002118:Calcium