Correlation of Sodium Channels Transcripts of Single DRG Neuron to their Electrophysiological and Pharmacological Profiles

Abstract

IntroductionVoltage gated sodium channels (VGSCs) play an important role in nociceptive transmission. They are implicated in the genesis and the conduction of the neuronal action potential firing. Four different isoforms (Nav1.3, Nav1.7, Nav1.8, and Nav1.9) have been linked to the nociceptive responses. However, their specifics implication on the genesis and transmission of the nociceptive response remain to be refined. The aim of this study is to achieve a better understanding of the synergy between the different isoforms in a single neuron that confer a unique electrophysiological profile to the neuron.HypothesisIntrinsic properties of the VGSCs isoform contribute to the electrophysiological profile of the small (<25μM) DRG neurons.MethodWe analyzed and correlated the composition of VGSCs in a single neuron and their electrophysiological properties. We used whole-cell configuration of the patch-clamp to record sodium currents or action potentials from acutely dissociated small DRG neurons from adult rats, before and after tetrodotoxin application, followed by a single-cell qPCR from the same neuron.Results and conclusionThere is a strong correlation between sodium currents and the mRNA quantification in single neuron. Voltage-clamp experiments show that TTX-S currents correlate with Nav1.7 mRNA transcripts and the TTX-R current correlate with Nav1.8 and Nav1.9 mRNA transcripts with correlations over 0.85. Current-clamp experiments show that Nav1.7 contributes to increase the overshoot, maximum rate of rise and the maximum decay (dv/dt max). Interestingly, the proportion of Nav1.7 and Nav1.8 were not implicated in the firing frequency of the neuron. Those results improve our current understanding on the specific implication of the different isoform on the electrophysiological profile of the small DRG neurons and have strong implication in the comprehension of the remodeling of VGSCs that occurs in different pathological pain.