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Molecular Identity of Dendritic Voltage-Gated Sodium Channels

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Science  14 May 2010:
Vol. 328, Issue 5980, pp. 906-909
DOI: 10.1126/science.1187958

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Counting Na+ Channels One by One

Understanding how nerve cells integrate their synaptic inputs and generate their output signals requires the identification of voltage-dependent ion channels on the axo-somato-dendritic surface of central neurons. Using improved ultrastructural immunocytochemistry techniques, Lorincz and Nusser (p. 906) found that a newly described voltage-gated sodium channel, Nav1.6, was present not only at nodes of Ranvier and axon initial segments but also at much lower, but functionally significant levels, in dendrites of CA1 pyramidal cells. However, other brain Na+ channels were not present in these dendrites, suggesting that dendritic sodium spikes result from somatic activation of this particular type of sodium channel.

Abstract

Active invasion of the dendritic tree by action potentials (APs) generated in the axon is essential for associative synaptic plasticity and neuronal ensemble formation. In cortical pyramidal cells (PCs), this AP back-propagation is supported by dendritic voltage-gated Na+ (Nav) channels, whose molecular identity is unknown. Using a highly sensitive electron microscopic immunogold technique, we revealed the presence of the Nav1.6 subunit in hippocampal CA1 PC proximal and distal dendrites. Here, the subunit density is lower by a factor of 35 to 80 than that found in axon initial segments. A gradual decrease in Nav1.6 density along the proximodistal axis of the dendritic tree was also detected without any labeling in dendritic spines. Our results reveal the characteristic subcellular distribution of the Nav1.6 subunit, identifying this molecule as a key substrate enabling dendritic excitability.

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