Figure 10.

Schematic illustration of dual roles of the VSOR Cl⁻ channel in mouse cortical neurons under excitotoxic conditions. The VSOR Cl⁻ channel is activated during excitotoxic glutamate stimulation and leads to formation of varicosities (process 1), and later to NVI (process 2) and necrotic cell death (process 3), by inducing NaCl influx in cooperation with GluR cation channels in both process 1 and 2, as well as with GABA_AR anion channels in process 1. The VSOR Cl⁻ channel is also activated after washout of glutamate and leads to resolution of varicosities (process 4) by inducing KCl efflux in cooperation presumably with K⁺ channels. GluR-mediated Ca²⁺ influx, which is known to be another key element of glutamate toxicity, is not included in this scheme.