1. Academic Validation
  2. Electrochemical sensor toolkit for simultaneous glutamate detection at edge of cleft and peri-soma

Electrochemical sensor toolkit for simultaneous glutamate detection at edge of cleft and peri-soma

  • Cell Chem Biol. 2025 Jun 19;32(6):885-898.e11. doi: 10.1016/j.chembiol.2025.05.002.
Jie Liu 1 Yuandong Liu 1 Dongmin Yin 2 Yang Tian 3
Affiliations

Affiliations

  • 1 School of Chemistry and Molecular Engineering, East China Normal University, Dongchuan Road 500, Shanghai 200241, China.
  • 2 Key Laboratory of Brain Functional Genomics, Ministry of Education and Shanghai, School of Life Science, East China Normal University, Shanghai 200062, China.
  • 3 School of Chemistry and Molecular Engineering, East China Normal University, Dongchuan Road 500, Shanghai 200241, China. Electronic address: ytian@chem.ecnu.edu.cn.
Abstract

Simultaneously monitoring glutamate (Glu) dynamic at edge of synaptic cleft and peri-soma is crucial for understanding Glu-related pathology. Here, we created an electrochemical Glu sensors toolkit with spatial resolution of ∼60 nm, combining biologically engineered Glu binding protein for specifically capturing Glu together with chemically designed ferrocene groups for signal labeling. Modulation conjugation approach between GluR and ferrocene significantly improved sensitivity up to 32-folds. More importantly, protein engineering of residue mutation and linker peptides flexibility expanded linear range from 10 μM to 6 mM, accelerated on/off times down to 35/40 ms. This toolkit realized real-time quantifying of Glu both at edge of cleft and peri-soma, we discovered that Glu was almost released through SLC7A11 channels in calyx of held synapse upon oxygen-glucose-deprivation, while Glu was mainly released through hemichannels upon β-amyloid42 stimulation. Our work provided a methodology for investigating Glu release and reuptake and offered insights for Glu related pathology.

Keywords

Alzheimer’s disease; SLC7A11; calyx of held; edge of cleft; electrochemical sensor; glutamate; hemichannels; nanoelectrode; neurotransmitter; oxygen glucose deprivation.

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