γ-氨基丁酸受体
同色
神经科学
酸敏离子通道
海马结构
离子通道
海马体
加巴能
γ-氨基丁酸
电生理学
化学
药理学
生物
受体
抑制性突触后电位
生物化学
蛋白质亚单位
基因
作者
Aleksandr P. Kalinovskii,Anton P. Pushkarev,Anastasia D. Mikhailenko,Denis S. Kudryavtsev,Olga A. Belozerova,Vladimir I. Shmygarev,Oleg N. Yatskin,Yuliya V. Korolkova,Sergey A. Kozlov,Dmitry I. Osmakov,Alexander Popov,Yaroslav A. Andreev
标识
DOI:10.3390/ijms241713148
摘要
Acid-sensing ion channels (ASICs) are proton-gated ion channels that mediate nociception in the peripheral nervous system and contribute to fear and learning in the central nervous system. Sevanol was reported previously as a naturally-occurring ASIC inhibitor from thyme with favorable analgesic and anti-inflammatory activity. Using electrophysiological methods, we found that in the high micromolar range, the compound effectively inhibited homomeric ASIC1a and, in sub- and low-micromolar ranges, positively modulated the currents of α1β2γ2 GABAA receptors. Next, we tested the compound in anxiety-related behavior models using a targeted delivery into the hippocampus with parallel electroencephalographic measurements. In the open field, 6 µM sevanol reduced both locomotor and θ-rhythmic activity similar to GABA, suggesting a primary action on the GABAergic system. At 300 μM, sevanol markedly suppressed passive avoidance behavior, implying alterations in conditioned fear memory. The observed effects could be linked to distinct mechanisms involving GABAAR and ASIC1a. These results elaborate the preclinical profile of sevanol as a candidate for drug development and support the role of ASIC channels in fear-related functions of the hippocampus.
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