Antisense oligonucleotide suppression of Na+/Ca2+ exchanger activity in primary neurons from rat brain

Ranciat-McComb, N.S.; Bland, Kimberly S.; Huschenbett, Jana; Ramonda, L.; Bechtel, Misty; Zaidi, Almas; Michaelis, Mary L.

doi:10.1016/s0304-3940(00)01524-x

Cited by 21 publications

(10 citation statements)

References 17 publications

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“…Analysis with fura-2 following brief glutamate activation demonstrated a rise in intracellular calcium that did not differ between the two groups. Recovery of intracellular calcium to baseline levels was significantly delayed in the NCX2 knockout mice, a finding consistent with Ranciat-McComb et al 36 This suggests that NCX2 is involved in the recovery to baseline of intracellular calcium following glutamate-induced depolarisation in hippocampal pyramidal cells. As noted above, Jeon et al 49 has also demonstrated larger focal infarcts in these animals following MCA occlusion.…”

Section: Transgenic Animal Studiessupporting

confidence: 87%

“…Antisense oligonucleotides against a conserved sequence of all three NCX isoforms resulted in higher baseline cytosolic calcium levels and a slower return to baseline following activation of calcium influx by NMDA. 36 These findings taken together, suggest that in depolarised and glucopenic cells NCX operates in calcium entry mode as predominately sodium extrusion occurs. As the energy state of the cell improves, and/or reperfusion occurs, the NCX operates in a protective rectifying calcium exit mode.…”

Section: Excitotoxicity Studiesmentioning

confidence: 90%

See 1 more Smart Citation

The role of the Na+/Ca2+ exchanger (NCX) in neurons following ischaemia

Jeffs

Meloni

Bakker

et al. 2007

Journal of Clinical Neuroscience

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Section: Transgenic Animal Studiessupporting

confidence: 87%

Section: Excitotoxicity Studiesmentioning

confidence: 90%

The role of the Na+/Ca2+ exchanger (NCX) in neurons following ischaemia

Jeffs

Meloni

Bakker

et al. 2007

Journal of Clinical Neuroscience

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“…Although PMCAs have higher affinity to Ca 2ϩ than do NCXs, the much lower turnover rate of PMCAs may cause quick saturation at elevated levels of Ca 2ϩ (10). The limited capacity of PMCAs suggests a more prominent role for NCXs in the process of rapid Ca 2ϩ extrusion; indeed, NCXs drive Ca 2ϩ extrusion after synaptic stimulation (11,12). In addition to the turnover rate, the capacity of a transporter molecule is determined by its density on the plasma membrane.…”

mentioning

confidence: 99%

Differential distribution of NCX1 contributes to spine–dendrite compartmentalization in CA1 pyramidal cells

Lőrincz

Rózsa

Katona

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Compartmentalization of Ca 2؉ between dendritic spines and shafts is governed by diffusion barriers and a range of Ca 2؉ extrusion mechanisms. The distinct contribution of different Ca 2؉ clearance systems to Ca 2؉ compartmentalization in dendritic spines versus shafts remains elusive. We applied a combination of ultrastructural and functional imaging methods to assess the subcellular distribution and role of NCX1 in rat CA1 pyramidal cells. Quantitative electron microscopic analysis of preembedding immunogold reactions revealed uniform densities of NCX1 along the shafts of apical and basal dendrites, but densities in dendritic shafts were approximately seven times higher than in dendritic spines. In line with these results, two-photon imaging of synaptically activated Ca 2؉ transients during NCX blockade showed preferential action localized to the dendritic shafts for NCXs in regulating spine-dendrite coupling.sodium-calcium exchange ͉ hippocampus ͉ ImmunoGold ͉ imaging H ippocampal pyramidal cells form glutamatergic synapses on dendritic spine heads. Imaging experiments using Ca 2ϩ sensitive dyes revealed that synaptic stimulation raised intracellular Ca 2ϩ to higher levels in spines than in dendrites, suggesting that spines are individual compartments able to accumulate Ca 2ϩ (1-3). This compartmentalization offers the basis for selective regulation of single synapses and synaptic plasticity.Several factors are involved in the compartmentalization of Ca 2ϩ into spines. Ca 2ϩ spatiotemporal dynamics is controlled by biophysical factors, inf lux, eff lux, buffers, pumps, and stores (4, 5). Synaptic activation restricts Ca 2ϩ inf lux to the spine head by activating NMDA receptors, Ca 2ϩ -permeable AMPA receptors, and voltage-gated Ca 2ϩ channels (6). Dendritic spine necks serve as diffusion barriers by separating the spine head from its parent dendrite (7,8), as demonstrated by the slow diffusion of endogenous Ca 2ϩ buffers and rapid Ca 2ϩ clearance through Ca 2ϩ -extrusion mechanisms (4, 5, 9). However, the distinct contribution of different extrusion mechanisms to Ca 2ϩ compartmentalization in dendritic spines versus shafts remains elusive. Na ϩ /Ca 2ϩ exchanger (NCX) and plasma membrane Ca 2ϩ -ATPase (PMCA) molecules play an essential role in Ca 2ϩ clearance across the plasma membrane in excitable cells (10). Although PMCAs have higher affinity to Ca 2ϩ than do NCXs, the much lower turnover rate of PMCAs may cause quick saturation at elevated levels of Ca 2ϩ (10). The limited capacity of PMCAs suggests a more prominent role for NCXs in the process of rapid Ca 2ϩ extrusion; indeed, NCXs drive Ca 2ϩ extrusion after synaptic stimulation (11,12). In addition to the turnover rate, the capacity of a transporter molecule is determined by its density on the plasma membrane. Distinct subcellular distributions could assign different roles to NCXs in Ca 2ϩ homeostasis along with their exposure to specifically located regulatory systems.There are three known NCX proteins (NCX1-3) encoded by different genes (13-15). Hippo...

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“…Under ischemic conditions, NCX3-deficient mice exhibit increased neuronal damage [13, 23]. Studies also showed that NCX plays a major role in restoring baseline Ca 2+ levels following glutamate-induced depolarization in cortical and hippocampal neurons [11, 24]. These findings highlight NCX function in the regulation of Na + and Ca 2+ following synaptic activity.…”

Section: Introductionmentioning

confidence: 99%

High levels of synaptosomal Na+–Ca2+ exchangers (NCX1, NCX2, NCX3) co-localized with amyloid-beta in human cerebral cortex affected by Alzheimer's disease

et al. 2011

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Synaptosomal expression of NCX1, NCX2, and NCX3, the three variants of the Na+-Ca2+ exchanger (NCX), was investigated in Alzheimer’s disease parietal cortex. Flow cytometry and immunoblotting techniques were used to analyze synaptosomes prepared from cryopreserved brain of cognitively normal aged controls and late stage Alzheimer’s disease patients. Major findings that emerged from this study are: (1) NCX1 was the most abundant NCX isoform in nerve terminals of cognitively normal patients; (2) NCX2 and NCX3 protein levels were modulated in parietal cortex of late stage Alzheimer’s disease: NCX2 positive terminals were increased in the Alzheimer’s disease cohort while counts of NCX3 positive terminals were reduced; (3) NCX1, NCX2 and NCX3 isoforms co-localized with amyloid-beta in synaptic terminals and all three variants are up-regulated in nerve terminals containing amyloid-beta. Taken together, these data indicate that NCX isoforms are selectively regulated in pathological terminals, suggesting different roles of each NCX isoform in Alzheimer’s disease terminals.

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Antisense oligonucleotide suppression of Na+/Ca2+ exchanger activity in primary neurons from rat brain

Cited by 21 publications

References 17 publications

The role of the Na+/Ca2+ exchanger (NCX) in neurons following ischaemia

The role of the Na+/Ca2+ exchanger (NCX) in neurons following ischaemia

Differential distribution of NCX1 contributes to spine–dendrite compartmentalization in CA1 pyramidal cells

High levels of synaptosomal Na+–Ca2+ exchangers (NCX1, NCX2, NCX3) co-localized with amyloid-beta in human cerebral cortex affected by Alzheimer's disease

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