title: Resurgent-like currents in mouse vas deferens myocytes are mediated by NaV1.6 voltage-gated sodium channels.
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 Na(V)1.6-null mice (Na(V)1.6(-/-)), lacking the expression of the Scn8a Na(+) channel gene, and their wild-type littermates (Na(V)1.6(+/+)). Na(V)1.6 immunoreactivity was clearly visible in dispersed smooth muscle cells obtained from Na(V)1.6(+/+), but not Na(V)1.6(-/-), 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 Na(V)1.6(+/+), but not Na(V)1.6(-/-), vas deferens myocytes. The resurgent-like current in Na(V)1.6(+/+) 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 Na(V)1.6 blocking toxin, purified from a crude mixture of TTX analogues by LC-FLD techniques, reversibly suppressed the resurgent-like currents. β-Pompilidotoxin, a voltage-gated Na(+) channel activator, evoked sustained resurgent-like currents in Na(V)1.6(+/+) but not Na(V)1.6(-/-) murine vas deferens myocytes. These results strongly indicate that, primarily, resurgent-like currents are generated as a result of Na(V)1.6 channel activity.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Saga University, Saga, 849-8501, Japan. noritera@cc.saga-u.ac.jp
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Teramoto
authors.forename: Hai-Lei
authors.initials: HL
authors.lastname: Zhu
authors.forename: Mari
authors.initials: M
authors.lastname: Yotsu-Yamashita
authors.forename: Tetsuichiro
authors.initials: T
authors.lastname: Inai
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Cunnane
mesh_terms: D000200:Action Potentials / Q000235:genetics; D000818:Animals; D019476:Insect Proteins / Q000494:pharmacology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D062557:NAV1.6 Voltage-Gated Sodium Channel / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014649:Vas Deferens / Q000166:cytology; D061585:Voltage-Gated Sodium Channel Agonists / Q000494:pharmacology; D061567:Voltage-Gated Sodium Channel Blockers / Q000494:pharmacology; D014862:Wasp Venoms / Q000494:pharmacology
chemical_list: D019476:Insect Proteins; D062557:NAV1.6 Voltage-Gated Sodium Channel; C491046:Scn8a protein, mouse; D061585:Voltage-Gated Sodium Channel Agonists; D061567:Voltage-Gated Sodium Channel Blockers; D014862:Wasp Venoms; C115329:pompilidotoxin beta; D013779:Tetrodotoxin