Function of KCNQ2 channels at nodes of Ranvier of lumbar spinal ventral nerves of rats.

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  • Author(s): Tonomura S;Tonomura S; Ling J; Ling J; Gu JG; Gu JG
  • Source:
    Molecular brain [Mol Brain] 2022 Jul 20; Vol. 15 (1), pp. 64. Date of Electronic Publication: 2022 Jul 20.
  • Publication Type:
    Journal Article; Research Support, N.I.H., Extramural
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: BioMed Central Country of Publication: England NLM ID: 101468876 Publication Model: Electronic Cited Medium: Internet ISSN: 1756-6606 (Electronic) Linking ISSN: 17566606 NLM ISO Abbreviation: Mol Brain Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : BioMed Central
    • Subject Terms:
      Ranvier's Nodes*/metabolism ; Spinal Nerves*; KCNQ2 Potassium Channel/*metabolism; Animals ; Electrophysiological Phenomena ; KCNQ2 Potassium Channel/genetics ; Membrane Potentials/physiology ; Patch-Clamp Techniques ; Rats
    • Abstract:
      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.
      (© 2022. The Author(s).)
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    • Grant Information:
      R01 DE023090 United States DE NIDCR NIH HHS; R01 NS109059 United States NS NINDS NIH HHS
    • Contributed Indexing:
      Keywords: Action potential; KCNQ2 channel; Kv7.2 channels; Motor nerves; Node of Ranvier; Saltatory conduction; Voltage-gated K+ channel
    • Accession Number:
      0 (KCNQ2 Potassium Channel)
      0 (Kcnq2 protein, rat)
    • Publication Date:
      Date Created: 20220720 Date Completed: 20220722 Latest Revision: 20240901
    • Publication Date:
      20240901
    • Accession Number:
      PMC9297653
    • Accession Number:
      10.1186/s13041-022-00949-0
    • Accession Number:
      35858950