Main Menu (Mobile)- Block

Main Menu - Block

Janelia scientists image voltage-gated sodium channels simultaneously in single neurons

custom | custom
custom | custom

07/12/22 | Janelia scientists image voltage-gated sodium channels simultaneously in single neurons

node:body | entity_field

A new study from the Liu Lab published in the Journal of Neuroscience directly observed for the first time two voltage-gated sodium channels simultaneously in single neurons, which could help uncover the distinct roles they play in sending signals in the central nervous system.

Voltage-gated sodium channels are critical for sending electrical signals between neurons so understanding more about their individual roles is important for decoding how signals are passed between cells. But distinguishing between these channels and where they are located in the cell is a major challenge in neuroscience. Because the channels are closely related, it is difficult to detect the individual channels through traditional methods.

The new research combined CRISPR-Cas9 genome editing, super-resolution and live-cell imaging to image two channels – Nav1.2 and Nav1.6 – allowing scientists to show the relationship between the two channels and why they behave differently.
 

A representative cultured hippocampal neuron with double labeling of Nav1.2 (V5, green) and Nav1.6 (HA, red) costained with Flag (blue).


The imaging and single-particle tracking allowed the researchers to identify a previously unknown mechanism targeting Nav1.2 to the distal axon of unmyelinated neurons. Nav1.6 was localized to the axon initial segment in myelinated neurons.
 

Airyscan image of Nav1.2 knock-in neurons (V5, green) in mouse cortex co-stained with MBP (red) shows its continuous distribution along distal axons without myelin coverage.

 

Airyscan image of Nav1.6 knock-in neurons (V5, green) in mouse cortex costained with MBP (red) shows its presence in myelinated neurons.


Understanding the distinct patterns of these channels could help scientists better understand their roles in the brain and how mutations linked to certain diseases affect their function.
 

 

Live-cell, single-molecule imaging of HaloTag-labeled Nav1.2 and Nav1.6 trafficking dynamics in cultured hippocampal neurons. Scale bar, 10 micron.

 

###

Citation

Hui Liu, Hong-Gang Wang, Geoffrey Pitt and Zhe Liu. “Direct Observation of Compartment-Specific Localization and Dynamics of Voltage-Gated Sodium Channels.” Journal of Neuroscience, published online July 13, 2022. doi: 10.1523/JNEUROSCI.0086-22.2022.