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• W2017027505 startingPage "1007" @default.
• W2017027505 abstract "Protein kinase A (PKA) has been reported to regulate synaptic αβγ γ-aminobutyric acid type A (GABA A ) receptor currents, but whether PKA regulates GABA A receptor peri- and extrasynaptic tonic currents is unknown. GABA A receptors containing α4 subunits are important in mediating tonic inhibition and exist as both α4βδ and α4βγ receptors in the brain. To mimic GABA-independent and GABA-dependent tonic currents, we transfected HEK 293T cells with α4β3δ or α4β3γ2L subunits and recorded spontaneous currents in the absence of applied GABA and steady-state currents in the presence of 1 μM GABA. Both α4β3δ and α4β3γ2L receptors displayed spontaneous currents, but PKA activation increased spontaneous α4β3δ currents substantially more than spontaneous α4β3γ2L currents. The increase in spontaneous α4β3δ currents was due to an increase in single-channel open frequency. In contrast, PKA activation did not alter steady-state tonic currents recorded in the presence of 1 μM GABA. We concluded that PKA had a GABA concentration–dependent effect on α4β3δ and α4β3γ2L currents. In the absence of GABA, spontaneous α4β3δ and, to a lesser extent, α4β3γ2L currents could provide a basal, tonic current that could be regulated by PKA. With increasing concentrations of extracellular GABA, however, tonic α4β3δ and α4β3γ2L currents would become more GABA dependent and less PKA sensitive. Thus in brain regions with fluctuating extracellular GABA levels, the dynamic range of GABA-activated tonic currents would be set by PKA and the increase in tonic current produced by increasing GABA would be reduced by PKA-mediated phosphorylation. When ambient GABA reaches micromolar concentrations, PKA would have no effect on steady-state tonic currents." @default.
• W2017027505 created "2016-06-24" @default.
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• W2017027505 date "2010-02-01" @default.
• W2017027505 modified "2023-10-01" @default.
• W2017027505 title "Modulation of Spontaneous and GABA-Evoked Tonic α4β3δ and α4β3γ2L GABA_A Receptor Currents by Protein Kinase A" @default.
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• W2017027505 doi "https://doi.org/10.1152/jn.00801.2009" @default.
• W2017027505 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2822691" @default.
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