Rapid AMPA desensitization in catfish cone horizontal cells

ArticleinVisual Neuroscience 14(1):13-8 · January 1997with4 Reads
DOI: 10.1017/S0952523800008713 · Source: PubMed
AMPA and NMDA type glutamate receptors were studied in isolated catfish cone horizontal cells using the whole-cell and outside-out patch-recording techniques. In whole-cell recordings, cyclothiazide (CTZ) enhanced the peak current in response to glutamate (in the presence of NMDA receptor antagonists). In patch recordings, currents evoked by rapid and maintained applications of glutamate desensitized with a time constant of one millisecond. CTZ blocked this rapid desensitization. Recovery from desensitization of the AMPA receptors was rapid, having a time constant of 8.65 ms. In contrast, the whole-cell and patch responses to applications of NMDA were much smaller than the AMPA receptor responses and did not desensitize. The relative contribution of these two receptor subtypes depends critically on the condition of the synapse; if glutamate levels are tonically present, the NMDA receptors contribute significantly to the postsynaptic response. If glutamate levels fall rapidly following the release of a single quantum of glutamate, then AMPA receptor currents will dominate the postsynaptic response.
    • "Functional CP-GluARs have been found in horizontal cells of every species investigated, including lizard (Jackman et al., 2011), fish (Eliasof and Jahr, 1997; Huang and Liang, 2005; Sun et al., 2010), skate (Kreitzer et al., 2009), and rabbit (Rivera et al., 2001; Figure 1B). Catfish cone horizontal cells, stellate neurons with enormous somata (Sakai and Naka, 1986), express extraordinarily fast CP-GluARs: in excised membrane patches at room temperature, glutamate-evoked currents desensitized with a time constant of ∼1 ms and recovered from desensitization with a time constant of less than 9 ms (Eliasof and Jahr, 1997). These rapid kinetics, rivaled only by GluARs receptors in avian auditory nuclei (Raman and Trussell, 1992), suggest that CP-GluARs may mediate local signaling in horizontal cell processes, because such brief conductances would be filtered strongly by the large membrane capacitance of the cell. "
    [Show abstract] [Hide abstract] ABSTRACT: The retina transforms light entering the eye into a sophisticated neural representation of our visual world. Specialized synapses, cells, and circuits in the retina have evolved to encode luminance, contrast, motion, and other complex visual features. Although a great deal has been learned about the cellular morphology and circuitry that underlies this image processing, many of the synapses in the retina remain incompletely understood. For example, excitatory synapses in the retina feature the full panoply of glutamate receptors, but in most cases specific roles for different receptor subtypes are unclear. In this brief review, I will discuss recent progress toward understanding how Ca(2+)-permeable AMPA receptors (CP-GluARs) contribute to synaptic transmission and newly discovered forms of synaptic plasticity in the retina.
    Full-text · Article · Sep 2011
    • "Rapid deactivation of GluA4-AMPARs helps lower the build-up of plateau potential and shorten the refractory period of APs, while fast recovery from desensitization of GluA4-AMPARs alleviates cumulative desensitization to minimize synaptic depression and strengthen synaptic potentials during repetitive activity (Joshi et al. 2004). Therefore, GluA4 is of vital importance for providing rapid and robust synaptic response, ultimately ensuring accurate conveyance of temporal codes required for the functionality at this auditory synapse and perhaps other fast central synapses (Silver et al. 1996; Eliasof & Jahr, 1997; Geiger et al. 1997). "
    [Show abstract] [Hide abstract] ABSTRACT: Fast excitatory synaptic transmission in central synapses is mediated primarily by AMPA receptors (AMPARs), which are heteromeric assemblies of four subunits, GluA1-4. Among these subunits, rapidly gating GluA3/4 appears to be the most abundantly expressed to enable neurotransmission with submillisecond precision at fast rates in subsets of central synapses. However, neither definitive identification of the molecular substrate for native AMPARs in these neurons, nor their hypothesized functional roles in vivo has been unequivocally demonstrated, largely due to lack of specific antagonists. Using GluA3 or GluA4 knockout (KO) mice, we investigated these issues at the calyx of Held synapse, which is known as a high-fidelity synapse involved in sound localization. Patch-clamp recordings from postsynaptic neurons showed that deletion of GluA4 significantly slowed the time course of both evoked and miniature AMPAR-mediated excitatory postsynaptic currents (AMPAR-EPSCs), reduced their amplitude, and exacerbated AMPAR desensitization and short-term depression (STD). Surprisingly, presynaptic release probability was also elevated, contributing to severe STD at GluA4-KO synapses. In contrast, only marginal changes in AMPAR-EPSCs were found in GluA3-KO mice. Furthermore, independent of changes in intrinsic excitability of postsynaptic neurons, deletion of GluA4 markedly reduced synaptic drive and increased action potential failures during high-frequency activity, leading to profound deficits in specific components of the auditory brainstem responses associated with synchronized spiking in the calyx of Held synapse and other related neurons in vivo. These observations identify GluA4 as the main determinant for fast synaptic response, indispensable for driving high-fidelity neurotransmission and conveying precise temporal information.
    Full-text · Article · Jun 2011
    • "AMPA receptors enter a desensitized state very rapidly (within several milliseconds) following application of glutamate (Kiskin et al., 1986; Patneau et al., 1993; Eliasof & Jahr, 1997). The present experiments were done using a superfusion system in which solutions were completely exchanged in about 20 ms, making it likely that the glutamate-induced responses reflect currents from largely desensitized receptors. "
    [Show abstract] [Hide abstract] ABSTRACT: Glutamate is believed to be the primary excitatory neurotransmitter in the vertebrate retina, and its fast postsynaptic effects are elicited by activating NMDA-, kainate-, or AMPA-type glutamate receptors. We have characterized the ionotropic glutamate receptors present on retinal horizontal cells of the skate, which possess a unique all-rod retina simplifying synaptic circuitry within the outer plexiform layer (OPL). Isolated external horizontal cells were examined using whole-cell voltage-clamp techniques. Glutamate and its analogues kainate and AMPA, but not NMDA, elicited dose-dependent currents. The AMPA receptor antagonist GYKI 52466 at 100 microm abolished glutamate-elicited currents. Desensitization of glutamate currents was removed upon coapplication of cyclothiazide, known to potentiate AMPA receptor responses, but not by concanavalin A, which potentiates kainate receptor responses. The dose-response curve to glutamate was significantly broader in the presence of the desensitization inhibitor cyclothiazide. Polyclonal antibodies directed against AMPA receptor subunits revealed prominent labeling of isolated external horizontal cells with the GluR2/3 and GluR4 antibodies. 1-Naphthylacetyl spermine, known to block calcium-permeable AMPA receptors, significantly reduced glutamate-gated currents of horizontal cells. Downregulation of glutamate responses was induced by increasing extracellular ion concentrations of Zn2+ and H+. The present study suggests that Ca2+-permeable AMPA receptors likely play an important role in shaping the synaptic responses of skate horizontal cells and that alterations in extracellular concentrations of calcium, zinc, and hydrogen ions have the potential to regulate the strength of postsynaptic signals mediated by AMPA receptors within the OPL.
    Full-text · Article · Sep 2009
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