The gap junction blockers carbenoxolone and 18β-glycyrrhetinic acid antagonize cone-driven light responses in the mouse retina

Yingqiu Xia, Scott Nawy

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Gap junctions are widely expressed throughout the retina, and play an important role in the processing of visual information. It has been proposed that horizontal cells express unpaired gap junctions, or hemichannels, in their dendrites, and that current flowing through hemichannels reduces transmembrane voltage at cone terminals, promoting the opening of Ca2+ channels near sites of transmitter release. This model predicts that pharmacological block of gap junctions should reduce the Ca2+ current at the equivalent cone voltage, thereby decreasing the postsynaptic light response. To test this prediction, and estimate the relative magnitude of this effect on third-order cells, we recorded light responses in mouse ganglion cells under photopic conditions and applied two gap junction antagonists, carbenoxolone and the structurally related 18β-glycyrrhetinic acid (GA). Both carbenoxolone and GA decreased the size of the light response to about 30% of control. Cells that were physiologically identified as ON, OFF, or ON/OFF were equally affected by carbenoxolone/GA. These gap junction blockers did not interfere with gamma-aminobutyric acid (GABA) or glutamate receptors, as they did not affect responses to direct activation of these receptors. Under control conditions, spots larger than 200 μm in diameter activated ganglion cell receptive-field surrounds. Comparing responses to small and large spots before and during carbenoxolone treatment, we found that carbenoxolone did not preferentially inhibit surround antagonism at the ganglion cell level, but instead scaled the responses to all spot sizes. Our results extend the findings of studies in lower vertebrates which showed that light responses in horizontal cells are decreased by carbenoxolone treatment, and support the idea that hemichannels in the outer retina, most likely on horizontal cells, constitute important gates that are critical for allowing light responses to move forward into the retinal circuit. Furthermore, it suggests that ganglion cell surrounds are generated in the inner retina.

Original languageEnglish (US)
Pages (from-to)429-435
Number of pages7
JournalVisual Neuroscience
Volume20
Issue number4
DOIs
StatePublished - Jul 1 2003

Fingerprint

Carbenoxolone
Glycyrrhetinic Acid
Gap Junctions
Retina
Light
Ganglia
GABA Receptors
Glutamate Receptors
Dendrites
Automatic Data Processing
Vertebrates
Pharmacology

Keywords

  • Carbenoxolone
  • Ganglion cell
  • Gap junction
  • Mouse retina

ASJC Scopus subject areas

  • Physiology
  • Sensory Systems

Cite this

The gap junction blockers carbenoxolone and 18β-glycyrrhetinic acid antagonize cone-driven light responses in the mouse retina. / Xia, Yingqiu; Nawy, Scott.

In: Visual Neuroscience, Vol. 20, No. 4, 01.07.2003, p. 429-435.

Research output: Contribution to journalArticle

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abstract = "Gap junctions are widely expressed throughout the retina, and play an important role in the processing of visual information. It has been proposed that horizontal cells express unpaired gap junctions, or hemichannels, in their dendrites, and that current flowing through hemichannels reduces transmembrane voltage at cone terminals, promoting the opening of Ca2+ channels near sites of transmitter release. This model predicts that pharmacological block of gap junctions should reduce the Ca2+ current at the equivalent cone voltage, thereby decreasing the postsynaptic light response. To test this prediction, and estimate the relative magnitude of this effect on third-order cells, we recorded light responses in mouse ganglion cells under photopic conditions and applied two gap junction antagonists, carbenoxolone and the structurally related 18β-glycyrrhetinic acid (GA). Both carbenoxolone and GA decreased the size of the light response to about 30{\%} of control. Cells that were physiologically identified as ON, OFF, or ON/OFF were equally affected by carbenoxolone/GA. These gap junction blockers did not interfere with gamma-aminobutyric acid (GABA) or glutamate receptors, as they did not affect responses to direct activation of these receptors. Under control conditions, spots larger than 200 μm in diameter activated ganglion cell receptive-field surrounds. Comparing responses to small and large spots before and during carbenoxolone treatment, we found that carbenoxolone did not preferentially inhibit surround antagonism at the ganglion cell level, but instead scaled the responses to all spot sizes. Our results extend the findings of studies in lower vertebrates which showed that light responses in horizontal cells are decreased by carbenoxolone treatment, and support the idea that hemichannels in the outer retina, most likely on horizontal cells, constitute important gates that are critical for allowing light responses to move forward into the retinal circuit. Furthermore, it suggests that ganglion cell surrounds are generated in the inner retina.",
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