Deep Sequencing of Somatosensory Neurons Reveals Molecular Determinants of Intrinsic Physiological Properties

Neuron. 2019 Aug 21;103(4):598-616.e7. doi: 10.1016/j.neuron.2019.05.039. Epub 2019 Jun 24.

Abstract

Dorsal root ganglion (DRG) sensory neuron subtypes defined by their in vivo properties display distinct intrinsic electrical properties. We used bulk RNA sequencing of genetically labeled neurons and electrophysiological analyses to define ion channel contributions to the intrinsic electrical properties of DRG neuron subtypes. The transcriptome profiles of eight DRG neuron subtypes revealed differentially expressed and functionally relevant genes, including voltage-gated ion channels. Guided by these data, electrophysiological analyses using pharmacological and genetic manipulations as well as computational modeling of DRG neuron subtypes were undertaken to assess the functions of select voltage-gated potassium channels (Kv1, Kv2, Kv3, and Kv4) in shaping action potential (AP) waveforms and firing patterns. Our findings show that the transcriptome profiles have predictive value for defining ion channel contributions to sensory neuron subtype-specific intrinsic physiological properties. The distinct ensembles of voltage-gated ion channels predicted to underlie the unique intrinsic physiological properties of eight DRG neuron subtypes are presented.

Keywords: DRG; RNA sequencing; genetic labeling; intrinsic membrane properties; mechanosensory neuron; somatosensation; transcriptome profile; voltage-gated ion channels.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Afferent Pathways / physiology
  • Animals
  • Computer Simulation
  • Ganglia, Spinal / cytology
  • Gene Expression Profiling
  • Gene Expression Regulation
  • High-Throughput Nucleotide Sequencing*
  • Ion Channels / biosynthesis
  • Ion Channels / genetics
  • Ion Channels / physiology*
  • Mechanoreceptors / physiology
  • Mice
  • Mice, Transgenic
  • Models, Neurological
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics
  • Patch-Clamp Techniques
  • Potassium Channels, Voltage-Gated / physiology
  • RNA / genetics
  • Sensory Receptor Cells / chemistry
  • Sensory Receptor Cells / classification
  • Sensory Receptor Cells / physiology*
  • Transcriptome

Substances

  • Ion Channels
  • Nerve Tissue Proteins
  • Potassium Channels, Voltage-Gated
  • RNA