Nitric Oxide Inactivation Mechanisms in the Brain: Role in Bioenergetics and Neurodegeneration
Figure 1
The major pathways of •NO production and inactivation in the brain. (a) •NO is synthesized following calcium entrance into the postsynaptic density (upon glutamate activation of NMDA receptors). Calcium activates nNOS by promoting Calmodulin (CaM) binding to the enzyme. •NO rapidly diffuses to neighboring tissue, being inactivated both by O2-dependent mechanisms and by scavenging by circulating erythrocytes (RBCs). (b) Typical electrochemical signals obtained using microelectrodes in the rat brain in vivo and in agarose gel following local application of small volumes (few nL) of •NO solution. First-order decay constant values (k) were used to quantify the decay profiles. (c) Anoxia, induced by a nitrite lethal dose, induced a 20% decrease in k (k2), in contrast with a large decrease in following cardiac arrest, suggesting that the major route of •NO inactivation in the brain in vivo is by circulating RBCs scavenging (k1). Adapted from [10].
