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Updated: Jun 19, 2026
10:29
Multi-photon Intracellular Sodium Imaging Combined with UV-mediated Focal Uncaging of Glutamate in CA1 Pyramidal Neurons
Published on: October 8, 2014
Subtype-selective targeting of voltage-gated sodium channels
Steve England1, Marcel J de Groot
1Pfizer Global Research and Development, Sandwich Laboratories, Kent, UK. steve.england@pfizer.com
British Journal of Pharmacology
|October 23, 2009
Summary
Voltage-gated sodium channels are crucial for nerve impulses. Developing subtype-selective drugs is challenging but structural biology offers future therapeutic design opportunities.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Voltage-gated sodium channels (VGSCs) are essential for action potential generation in excitable cells.
- Nine functional VGSC subtypes exist, exhibiting high sequence homology and similar properties.
- Genetic mutations in VGSCs are linked to various clinical conditions, highlighting their therapeutic relevance.
Purpose of the Study:
- To review the therapeutic potential of VGSCs as drug targets.
- To discuss the challenges in developing selective modulators for VGSC subtypes.
- To explore the emerging role of structural biology in future drug design.
Main Methods:
- Literature review of VGSC function, genetics, and pharmacology.
- Analysis of existing therapeutic strategies and their limitations.
- Discussion of advancements in electrophysiology and structural biology.
Main Results:
- Existing drugs targeting VGSCs show limited subtype selectivity and efficacy.
- High-throughput electrophysiology has faced challenges in identifying selective modulators.
- Structural biology, particularly with prokaryotic channels, is advancing understanding of VGSC structure.
Conclusions:
- Despite challenges, VGSCs remain important therapeutic targets.
- Subtype-selective modulators are needed for improved efficacy and toleration.
- Structural biology approaches hold promise for future structure-based drug design targeting VGSCs.
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01:24Non-gated Ion Channels
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