The Extracellular Zn²⁺ Concentration Surrounding Excited Neurons Is High Enough to Bind Amyloid‐β Revealed by a Nanowire Transistor

Abstract The Zn²⁺ stored in the secretory vesicles of glutamatergic neurons is coreleased with glutamate upon stimulation, resulting in the elevation of extracellular Zn²⁺ concentration (). This elevation of regulates the neurotransmission and facilitates the fibrilization of amyloid‐β (Aβ). However, the exact surrounding neurons under (patho)physiological conditions is not clear and the connection between and the Aβ fibrilization remains obscure. Here, a silicon nanowire field‐effect transistor (SiNW‐FET) with the Zn²⁺‐sensitive fluorophore, FluoZin‐3 (FZ‐3), to quantify the in real time is modified. This FZ‐3/SiNW‐FET device has a dissociation constant of ≈12 × 10⁻⁹m against Zn²⁺. By placing a coverslip seeded with cultured embryonic cortical neurons atop an FZ‐3/SiNW‐FET, the elevated to ≈110 × 10⁻⁹m upon stimulation with α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA). Blockers against the AMPA receptor or exocytosis greatly suppress this elevation, indicating that the Zn²⁺ stored in the synaptic vesicles is the major source responsible for this elevation of . In addition, a SiNW‐FET modified with Aβ could bind Zn²⁺ with a dissociation constant of ≈633 × 10⁻⁹m and respond to the Zn²⁺ released from AMPA‐stimulated neurons. Therefore, the can reach a level high enough to bind Aβ and the Zn²⁺ homeostasis can be a therapeutic strategy to prevent neurodegeneration.