title: Fast inhibition of glutamate-activated currents by caffeine.
abstract: BACKGROUND
  Caffeine stimulates calcium-induced calcium release (CICR) in many cell types. In neurons, caffeine stimulates CICR presynaptically and thus modulates neurotransmitter release.
  
  
  RESULTS
  Using the whole-cell patch-clamp technique we found that caffeine (20 mM) reversibly increased the frequency and decreased the amplitude of miniature excitatory postsynaptic currents (mEPSCs) in neocortical neurons. The increase in mEPSC frequency is consistent with a presynaptic mechanism. Caffeine also reduced exogenously applied glutamate-activated currents, confirming a separate postsynaptic action. This inhibition developed in tens of milliseconds, consistent with block of channel currents. Caffeine (20 mM) did not reduce currents activated by exogenous NMDA, indicating that caffeine block is specific to non-NMDA type glutamate receptors.
  
  
  CONCLUSIONS
  Caffeine-induced inhibition of mEPSC amplitude occurs through postsynaptic block of non-NMDA type ionotropic glutamate receptors. Caffeine thus has both pre and postsynaptic sites of action at excitatory synapses.
authors.affiliation: Division of Pulmonary & Critical Care Medicine, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Vyleta
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Smith
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008954:Models, Biological; D016202:N-Methylaspartate / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D018408:Patch-Clamp Techniques; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D015220:Calcium Channels; D000697:Central Nervous System Stimulants; D018377:Neurotransmitter Agents; D016194:Receptors, N-Methyl-D-Aspartate; D002110:Caffeine; D018698:Glutamic Acid; D016202:N-Methylaspartate; D002118:Calcium
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