Intracellular calcium elevation during plateau potentials mediated by extrasynaptic NMDA receptor activation in rat hippocampal CA1 pyramidal neurons is primarily due to calcium entry through voltage-gated calcium channels

摘要

We reported previously that plateau potentials mediated by extrasynaptic N-methyl-d-aspartate receptors (NMDARs) can be induced either by synaptic stimulation in the presence of glutamate transporter antagonist or by iontophoresis of NMDA in rat hippocampal CA1 pyramidal neurons. To examine whether the plateau potentials are accompanied by an elevation of intracellular Ca2+ and to determine the source of Ca2+ elevation, we performed Ca2+ imaging during the plateau potential. Neurons were loaded with Ca2+ indicator fluo-4, and the plateau potentials were generated either synaptically in the presence of glutamate transporter antagonist or by iontophoretically applying NMDA. We have found that a transient elevation in intracellular Ca2+ accompanies the plateau potential. The synaptically induced plateau potential and the Ca2+ elevation were blocked by 5,7-dichlorokynurenic acid (5,7-dCK), an antagonist for the glycine-binding sites of NMDAR. A mixture of Cd2+ and tetrodotoxin did not block NMDA-induced plateau potentials, but completely abolished the accompanying Ca2+ elevation in both the presence and absence of Mg2+ ions in the bathing solution. The NMDA-induced plateau potential was blocked by further adding 5,7-dCK. Our results show that the NMDAR-mediated plateau potential is accompanied by elevation of intracellular Ca2+ that is primarily caused by the influx of Ca2+ through voltage-gated Ca2+ channels. We reported previously that plateau potentials mediated by extrasynaptic NMDA receptors can be induced either by synaptic stimulation in the presence of glutamate transporter antagonist or by iontophoresis of NMDA in rat hippocampal CA1 pyramidal neurons. We found here that a transient elevation in intracellular Ca2+ accompanies the plateau potential and that the elevation of intracellular Ca2+ is caused primarily by the influx of Ca2+ through voltage-gated Ca2+ channels.