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Enhanced astroglial GABA uptake attenuates tonic GABAA inhibition of the presympathetic hypothalamic paraventricular nucleus neurons in heart failure

Overview of attention for article published in Journal of Neurophysiology, June 2015
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Title
Enhanced astroglial GABA uptake attenuates tonic GABAA inhibition of the presympathetic hypothalamic paraventricular nucleus neurons in heart failure
Published in
Journal of Neurophysiology, June 2015
DOI 10.1152/jn.00080.2015
Pubmed ID
Authors

Sudip Pandit, Ji Yoon Jo, Sang Ung Lee, Young Jae Lee, So Yeong Lee, Pan Dong Ryu, Jung Un Lee, Hyun-Woo Kim, Byeong Hwa Jeon, Jin Bong Park

Abstract

GABA generates persistent tonic inhibitory currents (Itonic) and conventional inhibitory postsynaptic currents in the hypothalamic paraventricular nucleus (PVN) via activation of GABAA receptors (GABAARs). We investigated the pathophysiological significance of astroglial GABA uptake in the regulation of Itonic in the PVN neurons projecting to the rostral ventrolateral medulla (PVN-RVLM). The Itonic of PVN-RVLM neurons were significantly reduced in heart failure (HF) compared with sham-operated (SHAM) rats. Reduced Itonic sensitivity to THIP argued for the decreased function of GABAAR δ subunits in HF, whereas similar Itonic sensitivity to benzodiazepines argued against the difference of γ2 subunit-containing GABAARs in SHAM and HF rats. HF Itonic 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 Itonic responses to bestrophin-1 blockade in SHAM and MI neurons further argued against a role for astroglial GABA release in HF Itonic 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 GABAARs function, the enhanced astroglial GABA uptake-induced attenuation of Itonic in HF PVN-RVLM neurons explains the deficit in tonic GABAergic inhibition and increased sympathetic outflow from the PVN during heart failure.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 36 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Egypt 1 3%
Unknown 35 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 19%
Researcher 6 17%
Professor 4 11%
Professor > Associate Professor 3 8%
Student > Doctoral Student 2 6%
Other 9 25%
Unknown 5 14%
Readers by discipline Count As %
Neuroscience 11 31%
Agricultural and Biological Sciences 6 17%
Medicine and Dentistry 6 17%
Biochemistry, Genetics and Molecular Biology 3 8%
Pharmacology, Toxicology and Pharmaceutical Science 2 6%
Other 3 8%
Unknown 5 14%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 June 2015.
All research outputs
#22,759,452
of 25,373,627 outputs
Outputs from Journal of Neurophysiology
#6,904
of 8,423 outputs
Outputs of similar age
#238,883
of 279,890 outputs
Outputs of similar age from Journal of Neurophysiology
#111
of 133 outputs
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