Pharmacological characterization, localization, and regulation of ionotropic glutamate receptors in skate horizontal cells

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.

Mechanisms of zinc modulation of olfactory bulb AMPA receptors

“…They concluded that the extracellular calcium concentration influences the effects of a high inhibitory (1 mM) but not a low potentiating (10 μM) concentration of zinc. These findings contrast with findings in skate retinal horizontal cells (Kreitzer et al, 2009). Kreitzer et al (2009) reported that inhibition of AMPAR-mediated responses to application of 100 μM glutamate by high concentrations of zinc (300 μM and 1 mM) was enhanced at lower extracellular concentrations of Ca2+ (0.2 mM Ringer's solution) (Kreitzer et al, 2009).…”

Functional properties of spontaneous excitatory currents and encoding of light/dark transitions in horizontal cells of the mouse retina

“…Similarly, AMPA and kainate receptor subunits were detected in the teleost retina (Peng et al, 1995;Vandenbranden et al, 2000;Klooster et al, 2001). These anatomical data apparently are in conflict with most electrophysiological studies, which report that only AMPA receptors contribute to the postsynaptic glutamate response (Yang et al, 1998;Blanco & de La Villa, 1999;Kreitzer et al, 2009). However, the functional presence of both AMPA and kainate receptors has been shown in human retinal horizontal cells (Shen et al, 2004).…”

“…As horizontal cell bodies do not generate Na + -dependent action potentials, changes in release kinetics modulate their membrane potential in a graded fashion. Most electrophysiological studies have found evidence for expression of AMPA receptors only (Yang et al, 1998;Blanco & de La Villa, 1999;Kreitzer et al, 2009), but immunocytochemical and ultrastructural data indicate the presence of both AMPA and kainate receptors at invaginating horizontal cell dendrites (Brandst€ atter et al, 1997;Hack et al, 2001).…”

Calcium-Permeable AMPA Receptors in the Retina

“…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).…”