The Extracellular Zn 2+ Concentration Surrounding Excited Neurons Is High Enough to Bind Amyloid‐β Revealed by a Nanowire Transistor

The Zn 2+ stored in the secretory vesicles of glutamatergic neurons is coreleased with glutamate upon stimulation, resulting in the elevation of extracellular Zn 2+ concentration ( C Z n 2 +e x). This elevation ofC Z n 2 +e xregulates the neurotransmission and facilitates the fibrilization of amyloid‐β (Aβ). However, the exactC Z n 2 +e xsurrounding neurons under (patho)physiological conditions is not clear and the connection betweenC Z n 2 +e xand the Aβ fibrilization remains obscure. Here, a silicon nanowire field‐effect transistor (SiNW‐FET) with the Zn 2+ ‐sensitive fluorophore, FluoZin‐3 (FZ‐3), to quantify theC Z n 2 +e xin real time is modified. This FZ‐3/SiNW‐FET device has a dissociation constant of ≈12 × 10 −9 m against Zn 2+ . By placing a coverslip seeded with cultured embryonic cortical neurons atop an FZ‐3/SiNW‐FET, theC Z n 2 +e xelevated to ≈110 × 10 −9 m 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 Zn 2+ stored in the synaptic vesicles is the major source responsible for this elevation ofC Z n 2 +e x. In addition, a SiNW‐FET modified with Aβ could bind Zn 2+ with a dissociation constant of ≈633 × 10 −9 m and respond to the Zn 2+ released from AMPA‐stimulated neurons. Therefore, theC Z n 2 +e xcan reach a level high enough to bind Aβ and the Zn 2+ homeostasis can be a therapeutic strategy to prevent neurodegeneration.