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Updated: Jun 9, 2026
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Patch Clamp Recordings on Intact Dorsal Root Ganglia from Adult Rats
Published on: September 29, 2016
GPR35 modulates NaV1.9 gating and sensory neuron excitability
Margaux Theys1, Jolien Vander Cruyssen1,2,3, Juan Salvatierra4,5
1Molecular Physiology and Neurophysics Group, Department of Basic and Applied Medical Sciences, University of Ghent, Ghent, Belgium.
British Journal of Pharmacology
|June 7, 2026
Summary
Researchers identified G protein-coupled receptor 35 (GPR35) as a regulator of the sodium channel NaV1.9 in sensory neurons. This discovery establishes a novel signaling pathway influencing neuronal excitability.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Voltage-gated sodium channel NaV1.9 is crucial for sensory neuron excitability.
- Upstream regulators, particularly G protein-coupled receptors (GPCRs), of NaV1.9 activity are not well understood.
Purpose of the Study:
- To identify novel GPCRs that modulate NaV1.9 function.
- To establish a receptor-channel signaling axis involving NaV1.9 in dorsal root ganglion (DRG) neurons.
Main Methods:
- Transcriptomic analysis of NaV1.9-expressing DRG neurons.
- Proximity ligation assays to assess protein interactions.
- Patch-clamp electrophysiology in primary mouse DRG neurons and a GPR35-deficient mouse model.
- Pharmacological activation of GPR35 using cromolyn disodium and investigation of cGMP-dependent pathways.
Main Results:
- GPR35 expression is enriched in NaV1.9-positive neurons, with both proteins showing spatial association.
- GPR35 activation potentiated NaV1.9 currents and increased neuronal excitability, effects dependent on GPR35 expression.
- cGMP-dependent signaling pathways also potentiated NaV1.9 currents in a GPR35-dependent manner.
- GPR35 activation partially attenuated inflammatory potentiation of NaV1.9 but did not normalize excitability.
Conclusions:
- GPR35 acts as a regulator of NaV1.9 in sensory neurons.
- A novel signaling module linking GPCR activation to NaV1.9 modulation of sensory neuron excitability is defined.
- This provides a mechanistic framework for understanding GPCR-NaV1.9 coupling.
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