Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9425777 | Neuroscience | 2005 | 11 Pages |
Abstract
Variations in intracellular calcium activity ([Ca2+]i) play crucial roles in information processing in Purkinje neurons such as synaptic plasticity. Although Na+-Ca2+ exchanger (NCX) has been shown to participate in the regulation of homeostasis and secretion in neuronal cells, the physiological role of NCX in Purkinje neurons, such as a role in cerebellar synaptic plasticity, is not well understood. NCX in acutely dissociated rat Purkinje neurons was identified by double staining with anti-calbindin D-28k antibody and anti-NCX antibody. The physiological activity of NCX was examined by measuring transient intracellular Ca2+ changes resulting from the Ca2+ influx via reverse mode of NCX (with 0 mM Na+/2.5 mM Ca2+ solutions) and the efflux via the forward mode of NCX (with 140 mM Na+/0 mM Ca2+ solutions). This transient increase in Ca2+ concentration was not elicited in the cells pretreated with NCX antisense oligodeoxynucleotides. And the Ca2+ influx resulting from the reverse mode of NCX was significantly reduced by 2-[2-[4-(4-nitrobenyloxy) phenyl] ethyl] isothiourea methanesulfonate, while the Ca2+ efflux via forward mode was inhibited by bepridil. The physiological role of NCX in synaptic function was studied by measuring Ca2+ transients induced by α-amino-3-hydroxy-5-methyl-4-isoxazolone-propionate (AMPA) receptor activation. This AMPA-evoked response was decreased with the inhibition of NCX forward mode and also, to less degree, with the inhibition of reverse mode. In antisense oligodeoxynucleotides pretreated cells, the AMPA-evoked response was also reduced, as was the case in NCX-inhibitor treated cells. The inhibition of NCX activity had depressant effects on Ca2+ transients induced by AMPA receptor activation. These results suggest that NCX plays a physiological role in modulating the activity of cerebellar Purkinje neurons, such as synaptic plasticity, via interaction with AMPA receptors in Purkinje neurons.
Keywords
PBS2,3-Dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamideDMEMHEPESKB-R7943NCXAMPAN-methyl-d-aspartic acidNMDANBQXBSADulbecco’s modified Eagle mediumNa+-Ca2+ exchangerAntisense oligodeoxynucleotides[Ca2+]ibovine serum albuminlong-term depressionBepridilintracellular Ca2+ concentrationLTDPhosphate-buffered salinePurkinje neuronAMPA receptor
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Authors
Y.T. Kim, Y.J. Park, S.Y. Jung, W.S. Seo, C.K. Suh,