Figure 1. Schematic representation of the anoxic depolarization in relation to ATP concentration and glutamate release.

Ischaemia causes depletion of intracellular ATP, which is thought to be important for inhibition of the Na⁺–K⁺ pump. Na⁺–K⁺ pump inhibition probably initiates membrane depolarization, as depicted in the lower cartoon of E_m. The putative timing of activation of NMDARs following a transient increase in glutamate release is indicated. NMDARs probably contribute to depolarization, but neuronal death is proposed to occur following activation of downstream cation channels such as pannexin-1 and TRPM7.