An integrative approach to the facile functional classification of dorsal root ganglion neuronal subclasses.
Animals
Calcium
/ metabolism
Conotoxins
/ pharmacology
Cytosol
/ metabolism
Ganglia, Spinal
/ cytology
Kv1.1 Potassium Channel
/ antagonists & inhibitors
Mice
Mice, Transgenic
Peptides
/ pharmacology
Potassium Channel Blockers
/ pharmacology
Sensory Receptor Cells
/ classification
Single-Cell Analysis
Transcriptome
DRG neurons
calcium imaging
conopeptide
neuronal subclasses
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
10 03 2020
10 03 2020
Historique:
pubmed:
23
2
2020
medline:
14
7
2020
entrez:
22
2
2020
Statut:
ppublish
Résumé
Somatosensory neurons have historically been classified by a variety of approaches, including structural, anatomical, and genetic markers; electrophysiological properties; pharmacological sensitivities; and more recently, transcriptional profile differentiation. These methodologies, used separately, have yielded inconsistent classification schemes. Here, we describe phenotypic differences in response to pharmacological agents as measured by changes in cytosolic calcium concentration for the rapid classification of neurons in vitro; further analysis with genetic markers, whole-cell recordings, and single-cell transcriptomics validated these findings in a functional context. Using this general approach, which we refer to as tripartite constellation analysis (TCA), we focused on large-diameter dorsal-root ganglion (L-DRG) neurons with myelinated axons. Divergent responses to the K-channel antagonist, κM-conopeptide RIIIJ (RIIIJ), reliably identified six discrete functional cell classes. In two neuronal subclasses (L1 and L2), block with RIIIJ led to an increase in [Ca]
Identifiants
pubmed: 32079727
pii: 1911382117
doi: 10.1073/pnas.1911382117
pmc: PMC7071849
doi:
Substances chimiques
Conotoxins
0
Peptides
0
Potassium Channel Blockers
0
kappaM-conotoxin RIIIK, Conus radiatus
0
dendrotoxin K
119128-61-9
Kv1.1 Potassium Channel
147173-20-4
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
5494-5501Subventions
Organisme : NIGMS NIH HHS
ID : P01 GM048677
Pays : United States
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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