title: Inhibition by pregnenolone sulphate, a metabolite of the neurosteroid pregnenolone, of voltage-gated sodium channels expressed in Xenopus oocytes.
abstract: Neurosteroids are known as allosteric modulators of the ligand-gated ion channel superfamily. Voltage-gated sodium channels (Na(v)) play an important role in mediating excitotoxic damages. Here we report the effects of neurosteroids on the function of Na(v), using voltage-clamp techniques in Xenopus oocytes expressed with the Na(v)1.2 α subunit. Pregnenolone sulphate, but not pregnenolone, inhibited sodium currents (I(Na)) at 3 - 100 μmol/L. The suppression of I(Na) by pregnenolone sulphate was due to increased inactivation with little change in activation. These findings suggest that pregnenolone sulphate, a metabolite of pregnenolone, suppresses the function of Na(v) via increased inactivation, which may contribute to the neuroprotection.
authors.affiliation: Department of Anesthesiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan. thori@med.uoeh-u.ac.jp
authors.forename: Takafumi
authors.initials: T
authors.lastname: Horishita
authors.forename: Susumu
authors.initials: S
authors.lastname: Ueno
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yanagihara
authors.forename: Yuka
authors.initials: Y
authors.lastname: Sudo
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Uezono
authors.forename: Dan
authors.initials: D
authors.lastname: Okura
authors.forename: Takeyoshi
authors.initials: T
authors.lastname: Sata
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D019314:Dehydroepiandrosterone Sulfate / Q000494:pharmacology; D005260:Female; D062551:NAV1.2 Voltage-Gated Sodium Channel / Q000502:physiology*; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D011284:Pregnenolone / Q000378:metabolism / Q000494:pharmacology*; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D014982:Xenopus laevis
chemical_list: D062551:NAV1.2 Voltage-Gated Sodium Channel; D026941:Sodium Channel Blockers; C018370:pregnenolone sulfate; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D011284:Pregnenolone