The Extracellular Zn Concentration Surrounding Excited Neurons Is High Enough to Bind Amyloid-β Revealed by a Nanowire Transistor.

The Zn stored in the secretory vesicles of glutamatergic neurons is coreleased with glutamate upon stimulation, resulting in the elevation of extracellular Zn concentration (CZn2+ex). This elevation of CZn2+ex regulates the neurotransmission and facilitates the fibrilization of amyloid-β (Aβ). However, the exact CZn2+ex surrounding neurons under (patho)physiological conditions is not clear and the connection between CZn2+ex and the Aβ fibrilization remains obscure. Here, a silicon nanowire field-effect transistor (SiNW-FET) with the Zn -sensitive fluorophore, FluoZin-3 (FZ-3), to quantify the CZn2+ex in real time is modified. This FZ-3/SiNW-FET device has a dissociation constant of ≈12 × 10 m against Zn . By placing a coverslip seeded with cultured embryonic cortical neurons atop an FZ-3/SiNW-FET, the CZn2+ex elevated to ≈110 × 10 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 stored in the synaptic vesicles is the major source responsible for this elevation of CZn2+ex. In addition, a SiNW-FET modified with Aβ could bind Zn with a dissociation constant of ≈633 × 10 m and respond to the Zn released from AMPA-stimulated neurons. Therefore, the CZn2+ex can reach a level high enough to bind Aβ and the Zn homeostasis can be a therapeutic strategy to prevent neurodegeneration.