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Articles

Presynaptic inhibition by GABA is mediated via two distinct GABA receptors with novel pharmacology

G Matthews, GS Ayoub and R Heidelberger
Journal of Neuroscience 1 March 1994, 14 (3) 1079-1090; DOI: https://doi.org/10.1523/JNEUROSCI.14-03-01079.1994
G Matthews
Department of Neurobiology and Behavior, State University of New York, Stony Brook 11794–5230.
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GS Ayoub
Department of Neurobiology and Behavior, State University of New York, Stony Brook 11794–5230.
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R Heidelberger
Department of Neurobiology and Behavior, State University of New York, Stony Brook 11794–5230.
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Abstract

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 GABAA-like Cl conductance and a GABAB- like inhibition of voltage-dependent Ca current. Both of the receptors underlying these actions have unusual pharmacology that fits neither GABAA nor GABAB classifications. The GABA-activated Cl conductance was not blocked by the classical GABAA antagonist bicuculline, while the inhibition of Ca current was neither mimicked by the GABAB agonist baclofen nor blocked by the GABAB antagonist 2-hydroxysaclofen. The “GABAC” 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 microM) than was the activation of the Cl conductance (K1/2 = 50 microM). Thus, by the criterion of being insensitive to both bicuculline and baclofen, both GABA receptors qualify as potential GABAC 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 GABAA and GABAB families, respectively.

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The Journal of Neuroscience: 14 (3)
Journal of Neuroscience
Vol. 14, Issue 3
1 Mar 1994
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Presynaptic inhibition by GABA is mediated via two distinct GABA receptors with novel pharmacology
G Matthews, GS Ayoub, R Heidelberger
Journal of Neuroscience 1 March 1994, 14 (3) 1079-1090; DOI: 10.1523/JNEUROSCI.14-03-01079.1994

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Presynaptic inhibition by GABA is mediated via two distinct GABA receptors with novel pharmacology
G Matthews, GS Ayoub, R Heidelberger
Journal of Neuroscience 1 March 1994, 14 (3) 1079-1090; DOI: 10.1523/JNEUROSCI.14-03-01079.1994
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