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.