{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T03:03:37Z","timestamp":1769310217570,"version":"3.49.0"},"reference-count":64,"publisher":"Maximum Academic Press","issue":"5","license":[{"start":{"date-parts":[[2009,6,2]],"date-time":"2009-06-02T00:00:00Z","timestamp":1243900800000},"content-version":"unspecified","delay-in-days":4292,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":["journals.cambridge.org"],"crossmark-restriction":true},"short-container-title":["Vis Neurosci"],"published-print":{"date-parts":[[1997,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>GABA is a major inhibitory neurotransmitter in the mammalian retina and it acts at many different sites<jats:italic>via<\/jats:italic>a variety of postsynaptic receptors. These include GABA<jats:sub>A<\/jats:sub>receptors and bicuculline-resistant GABA<jats:sub>C<\/jats:sub>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 GABA<jats:sub>A<\/jats:sub>and GABA<jats:sub>C<\/jats:sub>receptors. All three GABA antagonists stimulated ACh release by as much as ten-fold. By this measure, the<jats:italic>ED<jats:sub>50<\/jats:sub>s<\/jats:italic>for SR-95531, bicuculline, and picrotoxin were 0.8, 7.0, and 14 \u03bcM, respectively. Muscimol, a potent GABA<jats:sub>A<\/jats:sub>agonist, blocked the effects of SR-95531 and bicuculline, but not picrotoxin. This indicates that SR-95531 and bicuculline are competitive antagonists at the GABA<jats:sub>A<\/jats:sub>receptor, while picrotoxin blocks GABA<jats:sub>A<\/jats:sub>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 GABA<jats:sub>A<\/jats:sub>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 GABA<jats:sub>A<\/jats:sub>responses, possibly by also blocking GABA<jats:sub>C<\/jats:sub>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<jats:italic>ED<jats:sub>50<\/jats:sub>s<\/jats:italic>for SR-95531, bicuculline, and picrotoxin were 0.7 \u03bcM, 8 \u03bcM, and 94.6 \u03bcM, respectively. The results with SR-95531 and bicuculline indicate that GABA<jats:sub>A<\/jats:sub>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 GABA<jats:sub>C<\/jats:sub>receptors do not contribute to directional selectivity. This in turn suggests that feedforward GABA<jats:sub>A<\/jats:sub>inhibition, as opposed to feedback at bipolar terminals, is responsible for the null inhibition underlying directional selectivity.<\/jats:p>","DOI":"10.1017\/s0952523800011652","type":"journal-article","created":{"date-parts":[[2009,6,2]],"date-time":"2009-06-02T11:12:33Z","timestamp":1243941153000},"page":"939-948","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":47,"title":["Contributions of GABA<sub>A<\/sub>receptors and GABA<sub>C<\/sub>receptors to acetylcholine release and directional selectivity in the rabbit retina"],"prefix":"10.48130","volume":"14","author":[{"given":"Stephen C.","family":"Massey","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M.","family":"Linn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher 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