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• W2242804114 abstract "γ-Aminobutyric acid (GABA) generates persistent tonic inhibitory currents ( I tonic ) and conventional inhibitory postsynaptic currents in the hypothalamic paraventricular nucleus (PVN) via activation of GABA A receptors (GABA A Rs). We investigated the pathophysiological significance of astroglial GABA uptake in the regulation of I tonic in the PVN neurons projecting to the rostral ventrolateral medulla (PVN-RVLM). The I tonic of PVN-RVLM neurons were significantly reduced in heart failure (HF) compared with sham-operated (SHAM) rats. Reduced I tonic sensitivity to THIP argued for the decreased function of GABA A R δ subunits in HF, whereas similar I tonic sensitivity to benzodiazepines argued against the difference of γ 2 subunit-containing GABA A Rs in SHAM and HF rats. HF I tonic attenuation was reversed by a nonselective GABA transporter (GAT) blocker (nipecotic acid, NPA) and a GAT-3 selective blocker, but not by a GAT-1 blocker, suggesting that astroglial GABA clearance increased in HF. Similar and minimal I tonic responses to bestrophin-1 blockade in SHAM and HF neurons further argued against a role for astroglial GABA release in HF I tonic attenuation. Finally, the NPA-induced inhibition of spontaneous firing was greater in HF than in SHAM PVN-RVLM neurons, whereas diazepam induced less inhibition of spontaneous firing in HF than in SHAM neurons. Overall, our results showed that combined with reduced GABA A Rs function, the enhanced astroglial GABA uptake-induced attenuation of I tonic in HF PVN-RVLM neurons explains the deficit in tonic GABAergic inhibition and increased sympathetic outflow from the PVN during heart failure." @default.
• W2242804114 created "2016-06-24" @default.
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• W2242804114 date "2015-08-01" @default.
• W2242804114 modified "2023-10-17" @default.
• W2242804114 title "Enhanced astroglial GABA uptake attenuates tonic GABA_A inhibition of the presympathetic hypothalamic paraventricular nucleus neurons in heart failure" @default.
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• W2242804114 doi "https://doi.org/10.1152/jn.00080.2015" @default.
• W2242804114 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4533111" @default.
• W2242804114 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26063771" @default.
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