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Related Concept Videos

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FGF14 Peptide Derivative Differentially Regulates Nav1.2 and Nav1.6 Function.

Parsa Arman1, Zahra Haghighijoo1, Carmen A Lupascu2

  • 1Department of Pharmacology & Toxicology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555, USA.

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|September 27, 2025
PubMed
Summary
This summary is machine-generated.

A novel compound, ZL0177, selectively modulates voltage-gated sodium channels (Nav1.2 and Nav1.6), offering potential for targeted therapies. This study explores its isoform-specific effects on neuronal excitability and action potential discharge.

Keywords:
FGF14Nav1.2Nav1.6automated planar patch electrophysiologycentral nervous system (CNS)drug discoveryprotein–protein interaction (PPI)voltage-gated Na+ channel (Nav)

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Characterization of G Protein-coupled Receptors by a Fluorescence-based Calcium Mobilization Assay

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • Voltage-gated sodium channels (Nav) are crucial for neuronal electrical activity.
  • Specific isoforms like Nav1.2 and Nav1.6 are implicated in central nervous system development and channelopathies.
  • Modulation of Nav channels via protein-protein interactions (PPIs) presents a therapeutic avenue.

Purpose of the Study:

  • To investigate the isoform specificity of the peptidomimetic ZL0177 on Nav1.2 and Nav1.6 channels.
  • To determine the binding sites and physiological impact of ZL0177 on neuronal excitability.
  • To explore the potential of PPI derivatives for isoform-specific Nav channel regulation.

Main Methods:

  • Automated planar patch-clamp electrophysiology was employed to assess ZL0177's activity in cells expressing Nav1.2 or Nav1.6.
  • AlphaFold structural modeling was used to predict compound docking and binding sites.
  • Computational modeling was utilized to predict the effects of ZL0177 on action potential discharge.

Main Results:

  • ZL0177 suppressed sodium currents (INa) in both Nav1.2 and Nav1.6 expressing cells.
  • Functional effects on channel kinetics were isoform-specific, supported by differential compound docking.
  • Computational modeling predicted divergent effects on action potential discharge for Nav1.2 and Nav1.6.

Conclusions:

  • ZL0177 exhibits isoform-specific modulation of Nav1.2 and Nav1.6 channels.
  • PPI derivatives show promise for developing therapeutics targeting specific Nav channel isoforms.
  • This research opens avenues for novel treatments for channelopathies.