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Direction of action of presynaptic GABA receptors is highly dependent on the level of receptor activation.

08:00 EDT 20th March 2019 | BioPortfolio

Summary of "Direction of action of presynaptic GABA receptors is highly dependent on the level of receptor activation."

Many synapses, including parallel fiber synapses in the cerebellum, express presynaptic GABA receptors. However, reports of the functional consequences of presynaptic GABA receptor activation are variable across synapses, from inhibition to enhancement of transmitter release. We find that presynaptic GABA receptor function is bidirectional at parallel fiber synapses depending on GABA concentration and modulation of GABA receptors in mice. Activation of GABA receptors by low GABA concentrations enhances glutamate release, while activation of receptors by higher GABA concentrations inhibits release. Furthermore, blocking GABA receptors reduces GABA receptor currents and shifts presynaptic responses towards greater enhancement of release across a wide range of GABA concentrations. Conversely, enhancing GABA receptor currents with ethanol or neurosteroids shifts responses towards greater inhibition of release. The ability of presynaptic GABA receptors to enhance or inhibit transmitter release at the same synapse depending on activity level provides a new mechanism for fine control of synaptic transmission by GABA and may explain conflicting reports of presynaptic GABA receptor function across synapses.

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This article was published in the following journal.

Name: Journal of neurophysiology
ISSN: 1522-1598
Pages:

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Medical and Biotech [MESH] Definitions

A family of plasma membrane neurotransmitter transporter proteins that regulates that extracellular levels of the inhibitory neurotransmitter GAMMA-AMINOBUTYRIC ACID. They differ from GABA RECEPTORS, which signal cellular responses to GAMMA-AMINOBUTYRIC ACID. They control GABA reuptake into PRESYNAPTIC TERMINALS in the CENTRAL NERVOUS SYSTEM through high-affinity sodium-dependent transport.

Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and control an integral membrane chloride channel. GABA-A receptors are the most prevalent inhibitory neurotransmitter receptors in the brain. Several isoforms have been cloned, and they belong to a superfamily which includes nicotinic receptors, glycine receptors, and 5HT-3 receptors. Most GABA-A receptors have separate modulatory sites sensitive to benzodiazepines and to barbiturates.

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Drugs that bind to and activate GAMMA-AMINOBUTYRIC ACID receptors (RECEPTORS, GABA).

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