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Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
γ-aminobutyric acid type A receptors modulate neurosteroid binding to the voltage-dependent anion channel
1Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry of the Russian Academy of Sciences, Department of Kinetics of Chemical and Biological Processes, Laboratory for Biochemical and Cellular Studies, Chernogolovka, Russia.
Abstract:
Neurosteroids modulate the function of γ-aminobutyric acid type A (GABAA) receptors in the brain. We showed that GABAA receptors modulate neurosteroid interactions with VDAC. GABA enhanced [3H]6-AziP labeling of VDAC in a concentration-dependent manner. This effect of GABA was prevented by the GABAA receptor antagonists gabazine and picrotoxin. Studies with brain tissue from mice deficient for VDAC showed that GABA enhanced [3H]6-AziP labeling of VDAC2 and VDAC1. GABA enhanced photolabeling of VDAC in HEK cells expressing γ2L-subunit, suggesting that the γ2L-subunit is required for the interaction of GABAA receptors with VDAC. VDAC1 and VDAC2 both co-immunoprecipitated with GABAA receptors in rat brain membranes. Collectively, the data provide evidence for a direct signaling pathway between the synaptic plasma membrane GABAA receptor and VDAC, a mitochondrial outer membrane protein.
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