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Contributions of GABAA receptors and GABAC receptors to acetylcholine release and directional selectivity in the rabbit retina

Published online by Cambridge University Press:  02 June 2009

Stephen C. Massey ,
David M. Linn ,
Christopher A. Kittila  and
Wajid Mirza
Stephen C. Massey
Affiliation:
Department of Ophthalmology and Visual Science, University of Texas Medical School, Houston
David M. Linn
Affiliation:
LSU Eye Center and Neuroscience Center, LSU Medical School, New Orleans
Christopher A. Kittila
Affiliation:
Department of Ophthalmology and Visual Science, University of Texas Medical School, Houston
Wajid Mirza
Affiliation:
Department of Ophthalmology and Visual Science, University of Texas Medical School, Houston
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Abstract

GABA is a major inhibitory neurotransmitter in the mammalian retina and it acts at many different sites via a variety of postsynaptic receptors. These include GABAA receptors and bicuculline-resistant GABAC receptors. The release of acetylcholine (ACh) is inhibited by GABA and strongly potentiated by GABA antagonists. In addition, GABA appears to mediate the null inhibition which is responsible for the mechanism of directional selectivity in certain ganglion cells. We have used these two well-known examples of GABA inhibition to compare three GABA antagonists and assess the contributions of GABAA and GABAC receptors. All three GABA antagonists stimulated ACh release by as much as ten-fold. By this measure, the ED50s for SR-95531, bicuculline, and picrotoxin were 0.8, 7.0, and 14 μM, respectively. Muscimol, a potent GABAA agonist, blocked the effects of SR-95531 and bicuculline, but not picrotoxin. This indicates that SR-95531 and bicuculline are competitive antagonists at the GABAA receptor, while picrotoxin blocks GABAA responses by acting at a different, nonreceptor site such as the chloride channel. In the presence of a saturating dose of SR-95531 to completely block GABAA receptors, picrotoxin caused a further increase in the release of ACh. This indicates that picrotoxin potentiates ACh release by a mechanism in addition to the block of GABAA responses, possibly by also blocking GABAC receptors, which have been associated with bipolar cells. All three GABA antagonists abolished directionally selective responses from ON/OFF directional-selective (DS) ganglion cells. In this system, the ED50s for SR-95531, bicuculline, and picrotoxin were 0.7 μM, 8 μM, and 94.6 μM, respectively. The results with SR-95531 and bicuculline indicate that GABAA receptors mediate the inhibition responsible for directional selectivity. The addition of picrotoxin to a high dose of SR-95531 caused no further increase in firing rate. The comparatively high dose required for picrotoxin also suggests that GABAC receptors do not contribute to directional selectivity. This in turn suggests that feedforward GABAA inhibition, as opposed to feedback at bipolar terminals, is responsible for the null inhibition underlying directional selectivity.

Keywords

RetinaGABAACh releaseDirectional selectivitySR-95531BicucullinePicrotoxin
Type
Research Articles
Information
Visual Neuroscience , Volume 14 , Issue 5 , September 1997 , pp. 939 - 948
Copyright
Copyright © Cambridge University Press 1997

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