Bae, Yeonju Choi, Jae Hyouk Ryoo, Kanghyun Kim, Ajung Kwon, Osung Jung, Hyun-Gug Hwang, Eun Mi Park, Jae-Yong 2024-01-19T16:02:13Z 2024-01-19T16:02:13Z 2021-09-02 2020-12 1661-6596 https://pubs.kist.re.kr/handle/201004/117756 Astrocytes, the most abundant cell type in the brain, are non-excitable cells and play critical roles in brain function. Mature astrocytes typically exhibit a linear current-voltage relationship termed passive conductance, which is believed to enable astrocytes to maintain potassium homeostasis in the brain. We previously demonstrated that TWIK-1/TREK-1 heterodimeric channels mainly contribute to astrocytic passive conductance. However, the molecular identity of astrocytic passive conductance is still controversial and needs to be elucidated. Here, we report that spadin, an inhibitor of TREK-1, can dramatically reduce astrocytic passive conductance in brain slices. A series of gene silencing experiments demonstrated that spadin-sensitive currents are mediated by TWIK-1/TREK-1 heterodimeric channels in cultured astrocytes and hippocampal astrocytes from brain slices. Our study clearly showed that TWIK-1/TREK-1-heterodimeric channels can act as the main molecular machinery of astrocytic passive conductance, and suggested that spadin can be used as a specific inhibitor to control astrocytic passive conductance. English MDPI DOMAIN POTASSIUM-CHANNEL FUNCTIONAL HETERODIMERS GLIAL-CELLS TREK-1 LOCALIZATION EXPRESSION CLONING TASK-1 Spadin Modulates Astrocytic Passive Conductance via Inhibition of TWIK-1/TREK-1 Heterodimeric Channels Article 10.3390/ijms21249639 1 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.21, no.24 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 21 24 scie scopus 000602961800001 2-s2.0-85097814634 Biochemistry & Molecular Biology Chemistry, Multidisciplinary Biochemistry & Molecular Biology Chemistry Article DOMAIN POTASSIUM-CHANNEL FUNCTIONAL HETERODIMERS GLIAL-CELLS TREK-1 LOCALIZATION EXPRESSION CLONING TASK-1 astrocyte astrocytic passive conductance TWIK-1 TREK-1-heterodimeric channel spadin