APB suppresses synaptic input to retinal horizontal cells in fish: a direct action on horizontal cells modulated by intracellular pH

Abstract

1. Membrane potentials and cone-driven light responses were recorded from the H1-type horizontal cells in isolated retinas. Membrane potentials and intracellular pH were recorded also in enzymatically dissociated solitary horizontal cells. 2. In isolated retinas the glutamate analogue 2-amino-4-phosphonobutyrate (APB) hyperpolarized horizontal cells and reduced their light responses in a dose-dependent manner (5-200 microM). 3. The action of APB depended on the formulation of the saline; APB was effective in L-15 saline buffered with N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) but not in a commonly used, nominally CO2-free bicarbonate/Tris-buffered saline. 4. The major factor controlling the potency of APB was intracellular pH. APB was ineffective during retinal perfusion with NH4Cl-containing or CO2-free bicarbonate saline, both of which are known to alkalinize cells. In contrast, APB was effective in salines formulated to acidify the retinal neurons. These included both HEPES and Tris-buffered salines containing a weak acid and bicarbonate/Tris-buffered saline gassed with CO2. 5. APB reduced the size of glutamate-evoked depolarizations in solitary horizontal cells but had no independent action in the absence of glutamate. This reduction of glutamate-induced depolarization was observed in salines formulated to block voltage-dependent calcium and potassium currents. 6. The magnitude of APB's antagonistic action on solitary horizontal cells increased in a dose-dependent manner from 10 to 200 microM. The antagonism was increased by intracellular acidification and was reduced or eliminated by alkalinization. 7. We conclude that APB can reduce glutamate-evoked and, by inference, the photoreceptor neurotransmitter-evoked depolarization of horizontal cells by acting directly on the horizontal cells. This effect of APB is modulated by intracellular pH.

Expression of the mRNA of Seven Metabotropic Glutamate Receptors (mGluR1 to 7) in the Rat Retina. An In Situ Hybridization Study on Tissue Sections and Isolated Cells

“…On the other hand, from similar investigations in goldfish retina, Nawy et al (1989) reported that APB could suppress the transmission from cones to horizontal cells, and Takahashi and Copenhagen (1992) have recently demonstrated a direct action of APB on isolated goldfish horizontal cells. From these results, one would expect expression of a metabotropic receptor where APB has high potency, e.g.…”

Primate Retinal Signaling Pathways: Suppressingon-Pathway Activity in Monkey With Glutamate Analogues Mimics Human CSNB1-NYXGenetic Night Blindness

“…APB is a highly selective competitive antagonist at the mGluR6 receptor that localizes exclusively at the metabotropic G-proteincoupled synapse between rod and cone photoreceptors and their respective DBCs (Shiells et al 1981;Slaughter and Miller 1981). APB does not act at the chemical synapse onto HBCs, although it may alter horizontal feedback onto photoreceptors in some preparations (Hare and Owen 1992;Nawy et al 1989;Takahashi and Copenhagen 1992;Yang and Wu 1989).…”

A novel metabotropic glutamate receptor expressed in the retina and olfactory bulb

“…APB has been reported to antagonize the horizontal cell response to light (Nawy et al, 1989). This action could be caused by a presynaptic depression of transmitter release by photoreceptors, an antagonist effect on horizontal cell AMPA/kainate GluRs, or a modulation of these receptors or some other conductance through a second messenger pathway activated by APB and/or ACPD (Yang and Wu, 1991;Takahashi and Copenhagen, 1992).…”