Sensory neuron-derived Na<sub>V</sub>1.7 contributes to dorsal horn neuron excitability.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32128393.
- Also identified by DOI 10.1126/sciadv.aax4568 and PMC identifier 7030926.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Expression of the voltage-gated sodium channel Na<sub>V</sub>1.7 in sensory neurons is required for pain sensation. We examined the role of Na<sub>V</sub>1.7 in the dorsal horn of the spinal cord using an epitope-tagged Na<sub>V</sub>1.7 knock-in mouse. Immuno-electron microscopy showed the presence of Na<sub>V</sub>1.7 in dendrites of superficial dorsal horn neurons, despite the absence of mRNA. Rhizotomy of L5 afferent nerves lowered the levels of Na<sub>V</sub>1.7 in the dorsal horn. Peripheral nervous system-specific Na<sub>V</sub>1.7 null mutant mice showed central deficits, with lamina II dorsal horn tonic firing neurons more than halved and single spiking neurons more than doubled. Na<sub>V</sub>1.7 blocker PF05089771 diminished excitability in dorsal horn neurons but had no effect on Na<sub>V</sub>1.7 null mutant mice. These data demonstrate an unsuspected functional role of primary afferent neuron-generated Na<sub>V</sub>1.7 in dorsal horn neurons and an expression pattern that would not be predicted by transcriptomic analysis.
Medical subject headings
- NAV1.7 Voltage-Gated Sodium Channel
- Posterior Horn Cells
- Sensory Receptor Cells