Figure 4.

Inactivation of CaMKII via S-nitrosylation at Cys6 in the ischemic condition. In the normal condition (left panel), CaMKII and nNOS are controlled by glutamate signaling via NMDAR. Note that high levels of glutamate in the extracellular space are well known to occur early in the onset of ischemia, leading to the enhanced Ca²⁺ entry and the neuronal injury (right panel) [70]. At the same time, intracellular ATP concentration is decreased by mitochondrial impairment [67]. NO inhibits CaMKII activity via S-nitrosylation at Cys6 with ATP competitive fashion. S-nitrosylated CaMKII tends to be inhibited under the condition of low ATP concentration. This figure is an image of the postsynaptic hippocampal neuron where the mutual regulation of nNOS and CaMKII mainly exists.