Glutathione-induced sodium currents in neocortex

The present report demonstrates that glutathione (GSH), a tripeptide composed of glutamate, glycine and cysteine (gamma-L-glutamyl-L-cysteinyl-glycine) and best known as a free radical scavenger, elicits a large fast depolarizing potential when applied to cortical slices. This potential is maximally larger than that produced by either NMDA or AMPA. Like AMPA, the GSH current appears to be carried by sodium ions, but cannot be blocked by the glutamate receptor antagonists AP5 or DNQX. In addition, removal of external calcium or blockade of potassium currents by TEA does not diminish the GSH-induced potential. Together, these results suggest that GSH acts through its own receptor-mediated channels, independently of the known EAA receptors, and that its receptors may be a key, and previously unknown, component of cortical excitatory neurotransmission.