Summary:

The distribution of calcium in dendritic compartments of neurons is thought to be crucial in regulating postsynaptic function. The compartmentalized distribution of calcium offers the basis for selective regulation of single synapses and synaptic plasticity. Several mechanisms are known to contribute to the clearance of calcium from neurons, but the distinct contribution of different extrusion mechanisms to calcium compartmentalization in dendritic spines versus shafts remains elusive.

We used a novel combination of methods in order to explore the contribution of a Na+/Ca2+ exchanger (NCX) molecule in the calcium clearance across the plasma membrane in dendrites. High resolution, ultrastructural immunocytochemistry was combined with two-photon imaging to assess the subcellular distribution and role of NCX1 in rat CA1 pyramidal cells. NCX1 immunolabelling was predominantly found in the somatodendritic, but not along the axonal domain of pyramidal cells. Quantitative electron microscopic analysis of the preembedding immunogold reactions revealed comparable densities of NCX1 within dendritic shafts and spines sampled in different layers. However, the density of NCX1 in dendritic shafts was ~ 7 times higher than in dendritic spines and somata. In dendritic shafts a slight accumulation of gold particles was found around the base of spines, suggesting a role for NCX1 in the restriction of spatial spread of synaptic Ca2+ signals. In line with the relatively low density of NCX1 in spines, we could not detect significant changes in the decay kinetics of Ca2+ transients in dendritic spines, when NCX activity was inhibited during small intensity synaptic stimulation resulting in Ca2+ signals restricted to spines. The involvement of NCXs in Ca2+ extrusion was significant only at longer repetitive activation of synaptic NMDA receptors, producing a larger and longer Ca2+ influx to dendritic spines. Ca2+ transients could invade from spine to dendritic shafts only at long, repetitive synaptic activity, and the amplitude, decay time constant as well as the spatial spread of dendritic Ca2+ signals were increased in the presence of the NCX blocker benzamil.

Our results suggest a subcellular compartment-dependent distribution of NCX1 in the plasma membrane of CA1 pyramidal cells with preferential expression in dendritic shafts. Moreover, the distribution did not depend on the distance from the soma, thus our results also indicate a distance- and excitatory input-independent distribution of NCX1. Two-photon imaging of synaptically activated Ca2+ transients during NCX blockade showed preferential action localized to the dendritic shafts for NCXs in regulating spine-dendrite coupling.

FENS published it on its website in the "Scientific Highlight" section:

http://fens.org/shoty/?action=show&id=14

and also in the news section:

http://fens.org/news/?id=183