Function of KCNQ2 channels at nodes of Ranvier of lumbar spinal ventral nerves of rats.
Action potential
KCNQ2 channel
Kv7.2 channels
Motor nerves
Node of Ranvier
Saltatory conduction
Voltage-gated K+ channel
Journal
Molecular brain
ISSN: 1756-6606
Titre abrégé: Mol Brain
Pays: England
ID NLM: 101468876
Informations de publication
Date de publication:
20 07 2022
20 07 2022
Historique:
received:
01
06
2022
accepted:
07
07
2022
entrez:
20
7
2022
pubmed:
21
7
2022
medline:
23
7
2022
Statut:
epublish
Résumé
Previous immunohistochemical studies have shown the expression of KCNQ2 channels at nodes of Ranvier (NRs) of myelinated nerves. However, functions of these channels at NRs remain elusive. In the present study, we addressed this issue by directly applying whole-cell patch-clamp recordings at NRs of rat lumbar spinal ventral nerves in ex vivo preparations. We show that depolarizing voltages evoke large non-inactivating outward currents at NRs, which are partially inhibited by KCNQ channel blocker linopirdine and potentiated by KCNQ channel activator retigabine. Furthermore, linopirdine significantly alters intrinsic electrophysiological properties of NRs to depolarize resting membrane potential, increase input resistance, prolong AP width, reduce AP threshold, and decrease AP amplitude. On the other hand, retigabine significantly decreases input resistance and increases AP rheobase at NRs. Moreover, linopirdine increases excitability at NRs by converting single AP firing into multiple AP firing at many NRs. Saltatory conduction velocity is significantly reduced by retigabine, and AP success rate at high stimulation frequency is significantly increased by linopirdine. Collectively, KCNQ2 channels play a significant role in regulating intrinsic electrophysiological properties and saltatory conduction at NRs of motor nerve fibers of rats. These findings may provide insights into how the loss-of-function mutation in KCNQ2 channels can lead to neuromuscular disorders in human patients.
Identifiants
pubmed: 35858950
doi: 10.1186/s13041-022-00949-0
pii: 10.1186/s13041-022-00949-0
pmc: PMC9297653
doi:
Substances chimiques
KCNQ2 Potassium Channel
0
Kcnq2 protein, rat
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
64Subventions
Organisme : NINDS NIH HHS
ID : R01 NS109059
Pays : United States
Informations de copyright
© 2022. The Author(s).
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