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Isoliquiritigenin modulates the activity of LTS and non-LTS cells in the ventrolateral preoptic area via GABA(A) receptors

OBJECTIVE: Isoliquiritigenin (ILTG) is a chalcone compound that exhibits hypnotic effects via gamma-aminobutyric acid type A (GABA(A)) receptors. The ventrolateral preoptic area (VLPO) is a sleep-promoting center that contains a large number of GABA-releasing cells. There are two cell types in the V...

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Autores principales: Fan, Sumei, Jin, Qiaoling, Zhang, Pingping, Xu, Dejiao, Cheng, Juan, Wang, Liecheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10590785/
https://www.ncbi.nlm.nih.gov/pubmed/37876454
http://dx.doi.org/10.1016/j.heliyon.2023.e20620
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author Fan, Sumei
Jin, Qiaoling
Zhang, Pingping
Xu, Dejiao
Cheng, Juan
Wang, Liecheng
author_facet Fan, Sumei
Jin, Qiaoling
Zhang, Pingping
Xu, Dejiao
Cheng, Juan
Wang, Liecheng
author_sort Fan, Sumei
collection PubMed
description OBJECTIVE: Isoliquiritigenin (ILTG) is a chalcone compound that exhibits hypnotic effects via gamma-aminobutyric acid type A (GABA(A)) receptors. The ventrolateral preoptic area (VLPO) is a sleep-promoting center that contains a large number of GABA-releasing cells. There are two cell types in the VLPO: one generates a low-threshold spike (LTS), whereas the other lacks an LTS (non-LTS). METHOD: Whole-cell patch-clamp technology was used to detect the firing and currents of LTS and non-LTS cells in the VLPO. RESULTS: Bath administration of ILTG (10 μM) increased the firing rate of VLPO LTS cells, reversed by flumazenil (5 μM), a GABA(A) benzodiazepine site antagonist. However, the firing rate of VLPO non-LTS cells was inhibited by ILTG (10 μM), also reversed by flumazenil (5 μM). No differences were detected regarding resting membrane potential (RMP) amplitude, spike threshold, afterhyperpolarization (AHP) amplitude, or action potential duration (APD(50)) after ILTG (10 μM) perfusion in VLPO LTS cells. RMP amplitude was more hyperpolarized and spike threshold was higher after ILTG (10 μM) application in VLPO non-LTS cells. In addition, ILTG significantly reduced the frequency of miniature inhibitory postsynaptic currents (mIPSCs) in VLPO LTS cells. ILTG significantly increased the amplitude of mIPSCs in VLPO non-LTS cells. CONCLUSIONS: This study revealed that ILTG suppresses presynaptic GABA release on VLPO LTS cells, thereby increasing their excitability. ILTG enhances postsynaptic GABA(A) receptor function on VLPO non-LTS cells, thereby decreasing their excitability. These results suggest that ILTG may produce hypnotic effects by modulating the GABAergic synaptic transmission properties of these two cell types.
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spelling pubmed-105907852023-10-24 Isoliquiritigenin modulates the activity of LTS and non-LTS cells in the ventrolateral preoptic area via GABA(A) receptors Fan, Sumei Jin, Qiaoling Zhang, Pingping Xu, Dejiao Cheng, Juan Wang, Liecheng Heliyon Research Article OBJECTIVE: Isoliquiritigenin (ILTG) is a chalcone compound that exhibits hypnotic effects via gamma-aminobutyric acid type A (GABA(A)) receptors. The ventrolateral preoptic area (VLPO) is a sleep-promoting center that contains a large number of GABA-releasing cells. There are two cell types in the VLPO: one generates a low-threshold spike (LTS), whereas the other lacks an LTS (non-LTS). METHOD: Whole-cell patch-clamp technology was used to detect the firing and currents of LTS and non-LTS cells in the VLPO. RESULTS: Bath administration of ILTG (10 μM) increased the firing rate of VLPO LTS cells, reversed by flumazenil (5 μM), a GABA(A) benzodiazepine site antagonist. However, the firing rate of VLPO non-LTS cells was inhibited by ILTG (10 μM), also reversed by flumazenil (5 μM). No differences were detected regarding resting membrane potential (RMP) amplitude, spike threshold, afterhyperpolarization (AHP) amplitude, or action potential duration (APD(50)) after ILTG (10 μM) perfusion in VLPO LTS cells. RMP amplitude was more hyperpolarized and spike threshold was higher after ILTG (10 μM) application in VLPO non-LTS cells. In addition, ILTG significantly reduced the frequency of miniature inhibitory postsynaptic currents (mIPSCs) in VLPO LTS cells. ILTG significantly increased the amplitude of mIPSCs in VLPO non-LTS cells. CONCLUSIONS: This study revealed that ILTG suppresses presynaptic GABA release on VLPO LTS cells, thereby increasing their excitability. ILTG enhances postsynaptic GABA(A) receptor function on VLPO non-LTS cells, thereby decreasing their excitability. These results suggest that ILTG may produce hypnotic effects by modulating the GABAergic synaptic transmission properties of these two cell types. Elsevier 2023-10-12 /pmc/articles/PMC10590785/ /pubmed/37876454 http://dx.doi.org/10.1016/j.heliyon.2023.e20620 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Fan, Sumei
Jin, Qiaoling
Zhang, Pingping
Xu, Dejiao
Cheng, Juan
Wang, Liecheng
Isoliquiritigenin modulates the activity of LTS and non-LTS cells in the ventrolateral preoptic area via GABA(A) receptors
title Isoliquiritigenin modulates the activity of LTS and non-LTS cells in the ventrolateral preoptic area via GABA(A) receptors
title_full Isoliquiritigenin modulates the activity of LTS and non-LTS cells in the ventrolateral preoptic area via GABA(A) receptors
title_fullStr Isoliquiritigenin modulates the activity of LTS and non-LTS cells in the ventrolateral preoptic area via GABA(A) receptors
title_full_unstemmed Isoliquiritigenin modulates the activity of LTS and non-LTS cells in the ventrolateral preoptic area via GABA(A) receptors
title_short Isoliquiritigenin modulates the activity of LTS and non-LTS cells in the ventrolateral preoptic area via GABA(A) receptors
title_sort isoliquiritigenin modulates the activity of lts and non-lts cells in the ventrolateral preoptic area via gaba(a) receptors
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10590785/
https://www.ncbi.nlm.nih.gov/pubmed/37876454
http://dx.doi.org/10.1016/j.heliyon.2023.e20620
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