title: Fast interaction between AMPA and NMDA receptors by intracellular calcium.
abstract: Suppression of NMDA receptor (NMDAR)-mediated currents by intracellular Ca2+has been described as a negative feedback loop in NMDAR modulation. In the time scale of tenths of milliseconds the depth of the suppression does not depend on the Ca2+source. It may be caused by Ca2+influx through voltage-gated calcium channels, NMDAR channels or release from intracellular stores. However, NMDARs are often co-expressed in synapses with Ca2+-permeable AMPA receptors (AMPARs). Due to significant differences in activation kinetics between these two types of glutamate receptors (GluRs), Ca2+entry through AMPARs precedes full activation of NMDARs, and therefore, might have an impact on the amplitude of NMDAR-mediated currents. The study of Ca2+-mediated crosstalk between AMPAR and NMDAR in native synapses is challenging due to high NMDAR Ca2+permeability. Therefore, recombinant Ca2+-permeable AMPAR and Ca2+-impermeable NMDAR mutant channels were co-expressed in HEK 293 cells to examine their interaction. An AMPAR-mediated increase in intracellular Ca2+concentration ([Ca2+]i) reversibly reduced the size of NMDAR-mediated whole-cell currents. The time course of the NMDAR channel inactivation and recovery from inactivation followed the time course of the [Ca2+]itransient. When brief (1ms) pulses of glutamate were applied to outside-out patches, the degree of NMDAR inactivation increased with the increase in charge carried by the currents through co-activated AMPARs. However, AMPAR-mediated NMDAR inactivation was abolished in the presence of intracellular fast Ca2+buffer BAPTA or in Ca2+-free extracellular solution. We conclude that Ca2+entering through AMPARs inactivates co-localized NMDARs in the time range of excitatory postsynaptic currents.
authors.affiliation: OpenLab of Neurobiology, Kazan Federal University, 420111 Kazan, Russia; Department of Physiology and Pathophysiology, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Andrei
authors.initials: A
authors.lastname: Rozov
authors.affiliation: INMED, Institut de Neurobiologie de la Méditerranée UMR901, Marseille, France; Aix-Marseille Université, Marseille, France; INSERM U901, Marseille, France. Electronic address: nail.burnashev@inserm.fr.
authors.forename: Nail
authors.initials: N
authors.lastname: Burnashev
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D057809:HEK293 Cells; D006801:Humans; D018091:Receptors, AMPA / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
chemical_list: D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D002118:Calcium
keywords: Ca(2+)-induced inactivation; Ca(2+)-permeable AMPA receptor; Cross talk between receptors; NMDA receptor