GABA inhibits ACh release from the rabbit retina: a direct effect or feedback to bipolar cells?
The cholinergic amacrine cells of the rabbit retina may be labeled with [3H]-Ch and the activity of the cholinergic population monitored by following the release of [3H]-ACh. We have tested the effect of muscimol, a potent GABAA agonist, on (1) the light-evoked release of ACh, presumably mediated via bipolar cells, which are known to have a direct input to the cholinergic amacrine cells and (2) ACh release produced by exogenous glutamate analogs that probably have a direct effect on cholinergic amacrine cells. Muscimol blocked the light-evoked release of ACh with an IC50 of 1.0 microM. In contrast, ACh release produced by nonsaturating doses of kainate or NMDA was not reduced even by 100 microM muscimol. Thus, we have been unable to demonstrate a direct effect of GABA on the cholinergic amacrine cells. GABA antagonists, such as picrotoxin, caused a large increase in the base release and potentiated the light-evoked release of ACh. Both these effects were abolished by DNQX, a kainate antagonist that blocks the input to cholinergic amacine cells from bipolar cells. DNQX blocked the effects of picrotoxin even when controls showed that the mechanism of ACh release was still functional. Together, these results imply that the dominant site for the GABA-mediated inhibition of ACh release is on the bipolar cell input to the cholinergic amacrine cells. This is consistent with previous anatomical and physiological evidence that bipolar cells receive negative feedback from GABA amacrine cells.
Sensory Sciences Center, Graduate School of Biomedical Sciences, University of Texas Health Science Center, Houston 77030.
D M
DM
Linn
S C
SC
Massey
D000109:Acetylcholine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D018691:Excitatory Amino Acid Antagonists; D005246:Feedback; D005260:Female; D018756:GABA Antagonists; D018698:Glutamic Acid; D008027:Light; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D011810:Quinoxalines; D009118:Muscimol; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C056723:FG 9041; D000109:Acetylcholine