A tonic gamma-aminobutyric acid-mediated inhibition of cholinergic amacrine cells in rabbit retina.
Using the in vivo rabbit eyecup, we have studied the light-evoked release of acetylcholine (ACh) which is presumed to indicate the activity of cholinergic amacrine cells. Gamma-Aminobutyric acid (GABA) inhibited the light-evoked release of ACh (IC50 congruent to 1 mM), but the GABA antagonists bicuculline (5 micro M) and picrotoxin (20 micro M) potentiated the light-evoked release and markedly increased the resting release of ACh. This bicuculline/picrotoxin-evoked release was calcium dependent and the effects of bicuculline, but not picrotoxin, were blocked by muscimol, a potent GABA agonist. Muscimol also inhibited the light-evoked release of ACh (IC50 less than 1 micro M) and was at least 1000 times more potent than GABA. Nipecotic acid (1 mM), a GABA transport blocker, also inhibited the light-evoked release of ACh, but the effect was slow in onset and recovery was prompt. We conclude that the cholinergic amacrine cells of rabbit retina are inhibited by GABA. The relatively weak action of GABA, compared to muscimol, may be due to the presence of avid GABA transport systems. We ascribe the excitatory effects of bicuculline and picrotoxin to the antagonism of endogenous GABA, suggesting that the cholinergic cells are influenced by a tonic release of GABA. This is consistent with the effects of nipecotic acid. Although we are unable to specify the synaptic arrangements involved, we suggest that the most likely interaction is directly between GABA amacrine cells and the cholinergic amacrine cells and/or their presumed bipolar cell inputs.
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001640:Bicuculline / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D008297:Male; D010775:Photic Stimulation; D010852:Picrotoxin / Q000378:metabolism / Q000494:pharmacology; D011817:Rabbits; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology*
D000109:Acetylcholine; D001640:Bicuculline; D010852:Picrotoxin; D011950:Receptors, Cholinergic; D005680:gamma-Aminobutyric Acid