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Updated: May 13, 2026

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High Resolution Physical Characterization of Single Metallic Nanoparticles
Published on: June 28, 2019
A uniquely adaptable pore is consistent with NALCN being an ion sensor.
Adriano Senatore1, J David Spafford
1Department of Biology, University of Waterloo, Waterloo, ON, Canada.
Channels (Austin, Tex.)
|February 28, 2013
Summary
The NALCN ion channel has a unique, adaptable pore that changes selectivity for calcium or sodium ions. This suggests NALCN acts as a sensor for larger protein complexes, not a primary ion conductor.
Area of Science:
- Molecular Biology
- Ion Channel Physiology
- Evolutionary Biology
Background:
- NALCN is an orphan ion channel within the 4x6TM family, characterized by a conserved structure but a variable pore.
- Its pore exhibits distinct selectivity filters (calcium-like EEEE or sodium-like EEKE/EKEE) across different animal lineages.
- This adaptability challenges the notion of NALCN as a direct ion conductor.
Purpose of the Study:
- To investigate the functional role of the NALCN ion channel.
- To elucidate the mechanism behind NALCN's variable pore selectivity.
- To determine NALCN's interaction with other cellular components.
Main Methods:
- Analysis of NALCN's structural features and pore selectivity.
- Electrophysiological recordings in HEK-293T cells to assess ion conductance.
- Comparison of NALCN function with known 4x6TM channel sensor proteins.
Main Results:
- NALCN possesses a highly adaptable pore, differing in ion selectivity between radially and bilaterally symmetrical animals.
- Reported NALCN currents in HEK-293T cells were indistinguishable from leaky patch currents.
- Evidence suggests NALCN functions as a sensor coupled to the UNC80/UNC79 complex.
Conclusions:
- NALCN's variable pore is not consistent with a role in direct ion gating.
- NALCN likely functions as a sensor protein, modulating cellular responses based on ion flux.
- Its role as a sensor is analogous to other weakly conducting 4x6TM channel sensors like Nax.
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