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Mechanisms of presynaptic inhibition were examined in giant presynaptic terminals of retinal bipolar neurons, which receive GABAergic feedback synapses from amacrine cells. Two distinct inhibitory actions of GABA are present in the terminals: a GABA,-like Cl conductance and a GABA,-like inhibition of voltage-dependent Ca current. Both of the receptors underlying these actions have unusual pharmacology that fits neither GABA, nor GABA, classifications. The GABA-activated Cl conductance was not blocked by the classical GABA, antagonist bicuculline, while the inhibition of Ca current was neither mimicked by the GABA, agonist baclofen nor blocked by the GABA, antagonist 2-hydroxysaclofen. The "GABA," agonist cis-4-aminocrotonic acid (CACA) both activated the Cl conductance and inhibited Ca current, but the inhibition of Ca current was observed at much lower concentrations of CACA (< 1 MM) than was the activation of the Cl conductance (K,,, = 50 PM). Thus, by the criterion of being insensitive to both bicuculline and baclofen, both GABA receptors qualify as potential GA-BA, receptors. However, it is argued on functional grounds that the two GABA receptors coupled to Cl channels and to Ca channels are best regarded as members of the GABA, and GABA, families, respectively.

Isolated horizontal cells from goldfish retinas were prepared by enzymatic dissociation using papain and separated from other cells by velocity sedimentation. In the intact retina, H1 horizontal cells possess a high‐affinity mechanism for accumulating gamma‐aminobutyric acid (GABA). This property is retained in isolated cells, which also release the accumulated GABA in response to depolarization by elevated external K+. L‐Glutamic acid and its analogues are highly effective at micromolar concentrations in eliciting the release of preloaded GABA from isolated cells. At saturating concentrations, L‐aspartic acid stimulates about one‐third as much release as L‐glutamic acid. In contrast, the D‐isomers of glutamate and aspartate are ineffective. In the intact retina, micromolar concentrations of L‐glutamic acid analogues are also capable of eliciting GABA release from H1 horizontal cells. Release of the accumulated GABA from isolated H1 cells is largely independent of external Ca2+ concentrations. In the intact retina, H1 horizontal cells also possess a K+‐stimulated GABA release mechanism that is independent of the Ca2+ concentrations in the medium. In addition, there appears to be a small but significant amount of [3H]GABA release that may be Ca2+ dependent. Under our conditions, [3H]GABA release from isolated cells is unaffected by external Na+ concentrations between 20 and 120 mM. However, concentrations of 10 mM or less significantly diminishes this release, with 70% curtailed in Na+‐free solutions. Our results, together with morphological observations by a number of other investigators, suggest that there may be two distinct mechanisms for GABA release from goldfish H1 horizontal cells: one being a conventional vesicular mechanism which is Ca2+ dependent, while the other is Na+ driven and Ca2+ independent. H1 horizontal cells in the intact goldfish retina release the accumulated GABA in response to brief incubations in darkness, which is known to be the natural stimulus that depolarizes these neurones.

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