Astrocytic NHERF-1 Increases Seizure Susceptibility by Inhibiting Surface Expression of TREK-1.

ABSTRACT: 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

SUBMITTER: Bae Y 

PROVIDER: S-EPMC11845839 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature