The M-current works in tandem with the persistent sodium current to set the speed of locomotion.
Animals
Animals, Newborn
/ metabolism
Anthracenes
/ pharmacology
Central Pattern Generators
/ metabolism
KCNQ2 Potassium Channel
/ genetics
Locomotion
/ physiology
Male
Mice, Inbred C57BL
Motor Neurons
/ metabolism
Neurons
/ physiology
Potassium
/ metabolism
Potassium Channels
/ metabolism
Rats
Rats, Wistar
Sodium
/ metabolism
Sodium Channels
/ metabolism
Spinal Cord
/ physiology
Walking
/ physiology
Journal
PLoS biology
ISSN: 1545-7885
Titre abrégé: PLoS Biol
Pays: United States
ID NLM: 101183755
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
08
04
2020
accepted:
13
10
2020
revised:
25
11
2020
pubmed:
14
11
2020
medline:
5
1
2021
entrez:
13
11
2020
Statut:
epublish
Résumé
The central pattern generator (CPG) for locomotion is a set of pacemaker neurons endowed with inherent bursting driven by the persistent sodium current (INaP). How they proceed to regulate the locomotor rhythm remained unknown. Here, in neonatal rodents, we identified a persistent potassium current critical in regulating pacemakers and locomotion speed. This current recapitulates features of the M-current (IM): a subthreshold noninactivating outward current blocked by 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone dihydrochloride (XE991) and enhanced by N-(2-chloro-5-pyrimidinyl)-3,4-difluorobenzamide (ICA73). Immunostaining and mutant mice highlight an important role of Kv7.2-containing channels in mediating IM. Pharmacological modulation of IM regulates the emergence and the frequency regime of both pacemaker and CPG activities and controls the speed of locomotion. Computational models captured these results and showed how an interplay between IM and INaP endows the locomotor CPG with rhythmogenic properties. Overall, this study provides fundamental insights into how IM and INaP work in tandem to set the speed of locomotion.
Identifiants
pubmed: 33186352
doi: 10.1371/journal.pbio.3000738
pii: PBIOLOGY-D-20-00922
pmc: PMC7688130
doi:
Substances chimiques
10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone
0
Anthracenes
0
KCNQ2 Potassium Channel
0
Potassium Channels
0
Sodium Channels
0
Sodium
9NEZ333N27
Potassium
RWP5GA015D
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e3000738Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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