Non-ionotropic cross-talk between AMPA and NMDA receptors in rodent hippocampal neurones.
Many fast excitatory synapses in the hippocampus are enriched with both AMPARs (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate receptors) and NMDARs (N-methyl-D-aspartate receptors). Their proximity allows them to be activated simultaneously by the same neurotransmitter, L-glutamate. Activation of AMPARs leads to influx of sodium and calcium ions, which can increase or decrease NMDAR activity through sodium concentration-dependent cascades or a calcium-calmodulin-dependent inactivation process, respectively. Here we provide evidence that the activation of AMPARs inhibits NMDARs through a non-ionotropic mechanism. NMDA-induced current in isolated rat CA1 hippocampal cells and nucleated patches of cultured mouse hippocampal neurones decreased when AMPARs were activated. Conversely, when AMPARs were blocked, the NMDA component of glutamate-induced current increased. The inhibitory action of AMPAR activation on NMDAR-mediated current depends upon the open state of AMPA channels and rapidly diminishes after deactivation of AMPARs. The inhibitory action was independent of membrane voltage, univalent cation fluxes and calcium influx. The AMPA-NMDA cross-inhibition also occurred in evoked synaptic current in CA1 neurones from intact mouse hippocampal slices. This cross-talk may play a role in preventing overexcitation during bursting activities in the hippocampus.
Samuel Lunenfeld Research Institute, Mount Sinai Hospital and Institute of Medical Science, University of Toronto, 600 University Avenue, Toronto, Ontario, Canada M5G 1X5. donglin.bai@fmd.uwo.ca
Donglin
D
Bai
Robert U
RU
Muller
John C
JC
Roder
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D016202:N-Methylaspartate / Q000494:pharmacology; D009433:Neural Inhibition / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D020239:Receptor Cross-Talk / Q000502:physiology*; D018091:Receptors, AMPA / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
D018690:Excitatory Amino Acid Agonists; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D007608:Kainic Acid; D002118:Calcium