Spadin Modulates Astrocytic Passive Conductance via Inhibition of TWIK-1/TREK-1 Heterodimeric Channels
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 t...
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| Format: | Article |
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MDPI AG
2020-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/24/9639 |
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| author | Yeonju Bae Jae Hyouk Choi Kanghyun Ryoo Ajung Kim Osung Kwon Hyun-Gug Jung Eun Mi Hwang Jae-Yong Park |
| author_facet | Yeonju Bae Jae Hyouk Choi Kanghyun Ryoo Ajung Kim Osung Kwon Hyun-Gug Jung Eun Mi Hwang Jae-Yong Park |
| author_sort | Yeonju Bae |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T13:59:29Z |
| format | Article |
| id | doaj.art-d5b689d64f68464f82ce4cdec6430777 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T13:59:29Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d5b689d64f68464f82ce4cdec64307772023-11-21T01:21:48ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-012124963910.3390/ijms21249639Spadin Modulates Astrocytic Passive Conductance via Inhibition of TWIK-1/TREK-1 Heterodimeric ChannelsYeonju Bae0Jae Hyouk Choi1Kanghyun Ryoo2Ajung Kim3Osung Kwon4Hyun-Gug Jung5Eun Mi Hwang6Jae-Yong Park7School of Biosystems and Biomedical Sciences, College of Health Sciences, Korea University, Seoul 02841, KoreaCenter for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, KoreaSchool of Biosystems and Biomedical Sciences, College of Health Sciences, Korea University, Seoul 02841, KoreaCenter for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, KoreaSchool of Biosystems and Biomedical Sciences, College of Health Sciences, Korea University, Seoul 02841, KoreaSchool of Biosystems and Biomedical Sciences, College of Health Sciences, Korea University, Seoul 02841, KoreaCenter for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, KoreaSchool of Biosystems and Biomedical Sciences, College of Health Sciences, Korea University, Seoul 02841, KoreaAstrocytes, 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.https://www.mdpi.com/1422-0067/21/24/9639astrocyteastrocytic passive conductanceTWIK-1/TREK-1-heterodimeric channelspadin |
| spellingShingle | Yeonju Bae Jae Hyouk Choi Kanghyun Ryoo Ajung Kim Osung Kwon Hyun-Gug Jung Eun Mi Hwang Jae-Yong Park Spadin Modulates Astrocytic Passive Conductance via Inhibition of TWIK-1/TREK-1 Heterodimeric Channels International Journal of Molecular Sciences astrocyte astrocytic passive conductance TWIK-1/TREK-1-heterodimeric channel spadin |
| title | Spadin Modulates Astrocytic Passive Conductance via Inhibition of TWIK-1/TREK-1 Heterodimeric Channels |
| title_full | Spadin Modulates Astrocytic Passive Conductance via Inhibition of TWIK-1/TREK-1 Heterodimeric Channels |
| title_fullStr | Spadin Modulates Astrocytic Passive Conductance via Inhibition of TWIK-1/TREK-1 Heterodimeric Channels |
| title_full_unstemmed | Spadin Modulates Astrocytic Passive Conductance via Inhibition of TWIK-1/TREK-1 Heterodimeric Channels |
| title_short | Spadin Modulates Astrocytic Passive Conductance via Inhibition of TWIK-1/TREK-1 Heterodimeric Channels |
| title_sort | spadin modulates astrocytic passive conductance via inhibition of twik 1 trek 1 heterodimeric channels |
| topic | astrocyte astrocytic passive conductance TWIK-1/TREK-1-heterodimeric channel spadin |
| url | https://www.mdpi.com/1422-0067/21/24/9639 |
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