What question did this study set out to answer?

To determine whether dopamine directly modulates mammalian GABA_A receptors and to identify the specific subunit requirements and functional consequences of this interaction.

February 25, 2015Journal of NeuroscienceOpen Access

Dopamine Directly Modulates GABAAReceptors

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To determine whether dopamine directly modulates mammalian GABA_A receptors and to identify the specific subunit requirements and functional consequences of this interaction.
Conducted whole-cell patch-clamp electrophysiology in primary untransfected rat striatal neurons and recombinant HEK293 cells expressing defined GABA_A receptor subunit combinations.
Assayed dopamine concentrations ranging from 0.1 to 10 mM in the presence of tonic (1 μM) GABA or in the absence of GABA.
Tested pharmacological sensitivity using zinc-insensitive mutant β3 subunits (H267A) along with antagonists including picrotoxin, bicuculline, and gabazine.
Dopamine directly inhibited tonic-level (1 μM) GABA-evoked currents in native striatal neurons as well as recombinant α1β3 and α1β2γ2 receptors in HEK293 cells.
In the absence of GABA, dopamine directly activated α1β2γ2, α5β3γ2, and α1β3γ2 receptors, requiring β and γ subunits but not α subunits ((Z)β3γ2 EC50 = 660 μM).
Dopamine-mediated activation was fully blocked by picrotoxin but unaffected by competitive GABA_A antagonists, correlating strongly with spontaneous channel gating.

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Implication

Electrophysiological study uncovers direct dual modulation of GABA-A receptors by dopamine in rat striatal neurons, suggesting noncanonical monoamine control of neural inhibition.

Cite This Study

Hoerbelt et al. (2015) studied this question.

synapsesocial.com/papers/6a7cacb1704b28adc84c77ca https://doi.org/10.1523/jneurosci.4390-14.2015

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Implication

Electrophysiological study uncovers direct dual modulation of GABA-A receptors by dopamine in rat striatal neurons, suggesting noncanonical monoamine control of neural inhibition.

Dopamine Directly Modulates GABAAReceptors

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Implication

Cite This Study

Dopamine Directly Modulates GABAAReceptors

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Implication

Cite This Study

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