Differential modulation of NMDA-induced calcium transients by arachidonic acid and nitric oxide in cultured hippocampal neurons.

We have examined the effect of arachidonic acid on the transient increases in intracellular Ca 2 + evoked by NMDA and AMPA in cultured hippocampal pyramidal cells loaded with Fura-2 AM. Repeated brief pulses of NMDA elicited Ca 2 + transients that showed a modest run down. This run down was enhanced if the preparation was shielded from UV light and was reduced by conducting the experiments in the presence of the nitric oxide synthase inhibitor L-nitroarginine (100 μM). Arachidonic acid (2 μM) enhanced the Ca 2 + transients evoked by NMDA but not those evoked by AM PA. Other C20 unsaturated fatty acids did not alter the time course of the response to NMDA. These experiments suggest that elevated intracellular Ca 2 + activates nitric oxide synthase and the resulting synthesis of nitric oxide depresses the Ca 2 + response to NMDA while arachidonic acid augments these responses. Therefore two substances implicated in synaptic plasticity (arachidonic acid and nitric oxide) differentially modulate NMDA-mediated Ca 2 + entry into hippocampal neurons.