Modulation of presynaptic calcium homeostasis by nitric oxide

In the present work, we have adapted established microfluorimetric techniques based on the calcium indicator Fura-2, for the study of synaptosomal calcium homeostasis regulation in an immobilized synaptosomal preparation from the rat hippocampus. With this tool, we have addressed the actions of two proposed interneuronal messengers, nitric oxide (NO) and arachidonic acid (AA). NO donors (sodium nitroprusside, SNP and hydroxylamine, HX) and AA induced an increase in depolarization-induced calcium transients (both in magnitude and duration). However, resting calcium levels were not modified by NO, whereas AA application resulted in an steady increase in Ca. The effects of SNP were blocked when EGTA was present between depolarizations, suggesting that a minimum level of internal calcium load is required for NO effects. The effects of NO on Cai transients are persistent up to 90 min after drug application, and could be involved in some of the forms of synaptic plasticity where NO plays a role.