Veratridine produces distinct calcium response profiles in mouse Dorsal Root Ganglia neurons

Zainab A Mohammed,Ciara Doran,David Grundy,Mohammed A Nassar

doi:10.1038/srep45221

Abstract

Nociceptors are a subpopulation of dorsal root ganglia (DRG) neurons that detect noxious stimuli and signal pain. Veratridine (VTD) is a voltage-gated sodium channel (VGSC) modifier that is used as an “agonist” in functional screens for VGSC blockers. However, there is very little information on VTD response profiles in DRG neurons and how they relate to neuronal subtypes. Here we characterised VTD-induced calcium responses in cultured mouse DRG neurons. Our data shows that the heterogeneity of VTD responses reflects distinct subpopulations of sensory neurons. About 70% of DRG neurons respond to 30–100 μM VTD. We classified VTD responses into four profiles based upon their response shape. VTD response profiles differed in their frequency of occurrence and correlated with neuronal size. Furthermore, VTD response profiles correlated with responses to the algesic markers capsaicin, AITC and α, β-methylene ATP. Since VTD response profiles integrate the action of several classes of ion channels and exchangers, they could act as functional “reporters” for the constellation of ion channels/exchangers expressed in each sensory neuron. Therefore our findings are relevant to studies and screens using VTD to activate DRG neurons.

Highlights

Dorsal Root Ganglia (DRG) contain a heterogeneous population of sensory neurons that detect noxious and innocuous stimuli
The present study examined VTD-elicited calcium responses in cultured adult mouse dorsal root ganglia (DRG) neurons
We report that VTD response profiles correlated with soma size and with commonly used pharmacological markers of nociceptor

Summary

Introduction

Dorsal Root Ganglia (DRG) contain a heterogeneous population of sensory neurons that detect noxious and innocuous stimuli. DRG neurons that respond to noxious stimuli are known as nociceptors. Inflammation and nerve injury sensitise sensory neurons and result in hyperalgesia and allodynia[1,2]. Inflammation and injury-induced sensitisation of nociceptors is in part mediated through changes in expression and/or properties of VGSCs1–3. Drug screens for VGSC blockers use functional assays to test their sensitivity. These include FLIPR, calcium imaging and patch clamp electrophysiology; and employ Veratridine (VTD) as a VGSC “agonist” to test the pharmacological properties of candidate VGSC ligands[4]. Despite its wide use there is little information on how VTD responses relate to the different subpopulations of DRG neurons; nociceptors. A better characterisation of the VTD responses in DRG neurons may provide a novel functional classification of sensory neurons

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