Isoliquiritigenin modulates the activity of LTS and non-LTS cells in the ventrolateral preoptic area via GABAA receptors

Sumei Fan; Qiaoling Jin; Pingping Zhang; Dejiao Xu; Juan Cheng; Liecheng Wang

doi:10.1016/j.heliyon.2023.e20620

Isoliquiritigenin modulates the activity of LTS and non-LTS cells in the ventrolateral preoptic area via GABA_A receptors

Heliyon. 2023 Oct 12;9(10):e20620. doi: 10.1016/j.heliyon.2023.e20620. eCollection 2023 Oct.

Authors

Sumei Fan^{1

2}, Qiaoling Jin², Pingping Zhang², Dejiao Xu², Juan Cheng², Liecheng Wang^{1

2

3}

Affiliations

¹ Department of Anatomy and Histoembryology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China.
² Department of Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China.
³ School of Stomatology, Anhui Medical University, Hefei, Anhui, China.

Abstract

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 (APD₅₀) 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.

Keywords: Electrophysiological experiments; Gamma-aminobutyric acid type A receptors; Isoliquiritigenin; LTS cells; Non-LTS cells; The ventrolateral preoptic area.