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

The Zn2+ stored in the secretory vesicles of glutamatergic neurons is coreleased with glutamate upon stimulation, resulting in the elevation of extracellular Zn2+ concentration (CZn ex 2+). This elevation of CZn ex 2+ regulates the neurotransmission and facilitates the fibrilization of amyloid-β (Aβ). However, the exact +Znex C 2 surrounding neurons under (patho)physiological conditions is not clear and the connection between +Znex C 2 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 CZn ex 2+ in real time is modified.This FZ-3/SiNW-FET device has a dissociation constant of ≈12 × 10−9 m against Zn2+. By placing a coverslip seeded with cultured embryonic cortical neurons atop an FZ-3/SiNW-FET, the CZn ex 2+ elevated 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 Zn2+ stored in the synaptic vesicles is the major source responsible for this elevation of +
Zn exC 2 . In addition, a SiNW-FET modified with Aβ could bind Zn2+ with a dissociation constant of ≈633 × 10−9 m and respond to the Zn2+ released from AMPA-stimulated neurons. Therefore, the CZn ex 2+ can reach a level high enough to bind Aβ and the Zn2+ homeostasis can be a therapeutic strategy to prevent neurodegeneration.