Resurgent-like currents in mouse vas deferens myocytes are mediated by NaV1.6 voltage-gated sodium channels

Noriyoshi Teramoto, Hai Lei Zhu, Mari Yotsu-Yamashita, Tetsuichiro Inai, Thomas C. Cunnane

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Patch-clamp experiments were performed to investigate the molecular properties of resurgent-like currents in single smooth muscle cells dispersed from mouse vas deferens, utilizing both NaV1.6-null mice (Na V1.6-/-), lacking the expression of the Scn8a Na + channel gene, and their wild-type littermates (Na V1.6+/+). NaV1.6 immunoreactivity was clearly visible in dispersed smooth muscle cells obtained from NaV1.6+/+, but not NaV1.6+/+, vas deferens. Following a depolarization to +30 mV from a holding potential of +70 mV (to produce maximal inactivation of the Na+ current), repolarization to voltages between -60 and +20 mV elicited a tetrodotoxin (TTX)- sensitive inward current in NaV1.6+/+, but not NaV1.6-/-, vas deferens myocytes. The resurgent-like current in NaV1.6+/+ vas deferens myocytes peaked at approximately +20 mV in the current-voltage relationship. The peak amplitude of the resurgent-like current remained at a constant level when the membrane potential was repolarized to +20 mV following the application of depolarizing rectangular pulses to more positive potentials than -20 mV. 4,9-Anhydrotetrodotoxin (4,9-anhydroTTX), a selective NaV1.6 blocking toxin, purified from a crude mixture of TTX analogues by LCFLD techniques, reversibly suppressed the resurgent-like currents. β-Pompilidotoxin, a voltage-gated Na+ channel activator, evoked sustained resurgent-like currents in Na V1.6+/+ but not NaV1.6-/- murine vas deferens myocytes. These results strongly indicate that, primarily, resurgent-like currents are generated as a result of NaV1.6 channel activity.

Original languageEnglish
Pages (from-to)493-502
Number of pages10
JournalPflugers Archiv European Journal of Physiology
Volume464
Issue number5
DOIs
Publication statusPublished - 2012 Nov

Keywords

  • Na channels
  • Na1.6
  • Resurgent-like currents
  • Scn8a
  • Smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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