Bae, Yeonju Lee, Soomin Kim, Ajung Lee, Shinae Kim, Seong­Seop Park, Sunyoung Noh, Junyeol Ryoo, Kanghyun Yi, Gwan­Su Park, Jae­Yong Hwang, Eun Mi 2024-11-20T06:30:05Z 2024-11-20T06:30:05Z 2024-11-19 2025-04 0894-1491 https://pubs.kist.re.kr/handle/201004/151113 Mature hippocampal astrocytes exhibit a linear current-to-voltage (I-V) K+ membrane conductance called passive conductance. It is estimated to enable astrocytes to keep potassium homeostasis in the brain. We previously reported that the TWIK-1/TREK-1 heterodimeric channels are crucial for astrocytic passive conductance. However, the regulatory mechanism of these channels by other binding proteins remains elusive. Here, we identified Na+/H+ exchange regulator-1 (NHERF-1), a protein highly expressed in astrocytes, as a novel interaction partner for these channels. NHERF-1 endogenously bound to TWIK-1/TREK-1 in hippocampal cultured astrocytes. When NHERF-1 is overexpressed or silenced, surface expression and activity of TWIK-1/TREK-1 heterodimeric channels are inhibited or enhanced, respectively. Furthermore, we confirmed that reduced astrocytic passive conductance by NHERF-1 overexpressing in the hippocampus increases kainic acid (KA)-induced seizure sensitivity. Taken together, these results suggest that NHERF-1 is a key regulator of TWIK-1/TREK-1 heterodimeric channels in astrocytes and suppression of TREK-1 surface expression by NHERF-1 increases KA-induced seizure susceptibility via reduction of astrocytic passive conductance. English John Wiley & Sons Inc. Astrocytic NHERF-1 Increases Seizure Susceptibility by Inhibiting Surface Expression of TREK-1 Article 10.1002/glia.24644 1 GLIA, v.73, no.4, pp.720 - 736 GLIA 73 4 720 736 N scie scopus 001357207200001 Neurosciences Neurosciences & Neurology Article CONDUCTANCE MODULATION LOCALIZATION PROTEINS COFACTOR TWIK-1 PDZ-SCAFFOLD POTASSIUM CHANNEL DOMAIN astrocytic passive conductance kainic acid-induced seizures NHERF-1 TREK-1