title: Inhibition of veratridine-induced delayed inactivation of the voltage-sensitive sodium channel by synthetic analogs of crambescin B.
abstract: Crambescin B carboxylic acid, a synthetic analog of crambescin B, was recently found to inhibit the voltage-sensitive sodium channels (VSSC) in a cell-based assay using neuroblastoma Neuro 2A cells. In the present study, whole-cell patch-clamp recordings were conducted with three heterologously expressed VSSC subtypes, Nav1.2, Nav1.6 and Nav1.7, in a human embryonic kidney cell line HEK293T to further characterize the inhibition of VSSC by crambescin B carboxylic acid. Contrary to the previous observation, crambescin B carboxylic acid did not inhibit peak current evoked by depolarization from the holding potential of -100mV to the test potential of -10mV in the absence or presence of veratridine (VTD). In the presence of VTD, however, crambescin B carboxylic acid diminished VTD-induced sustained and tail currents through the three VSSC subtypes in a dose-dependent manner, whereas TTX inhibited both the peak current and the VTD-induced sustained and tail currents through all subtypes of VSSC tested. We thus concluded that crambescin B carboxylic acid does not block VSSC in a similar manner to TTX but modulate the action of VTD, thereby causing an apparent block of VSSC in the cell-based assay.
authors.affiliation: Graduate School of Agricultural Science, Tohoku University, Aoba, Sendai 981-8555, Japan.
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Tsukamoto
authors.affiliation: Graduate School of Agricultural Science, Tohoku University, Aoba, Sendai 981-8555, Japan.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Chiba
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Nakazaki
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ishikawa
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Nakane
authors.affiliation: Graduate School of Dentistry, Tohoku University, Aoba, Sendai 980-8575, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Cho
authors.affiliation: Graduate School of Agricultural Science, Tohoku University, Aoba, Sendai 981-8555, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Yotsu-Yamashita
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Nishikawa
authors.affiliation: Graduate School of Dentistry, Tohoku University, Aoba, Sendai 980-8575, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Wakamori
authors.affiliation: Graduate School of Agricultural Science, Tohoku University, Aoba, Sendai 981-8555, Japan. Electronic address: konoki@m.tohoku.ac.jp.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Konoki
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D013141:Spiro Compounds / Q000737:chemistry / Q000494:pharmacology*; D014701:Veratridine / Q000737:chemistry* / Q000494:pharmacology; D061567:Voltage-Gated Sodium Channel Blockers / Q000737:chemistry / Q000494:pharmacology; D061566:Voltage-Gated Sodium Channels / Q000187:drug effects*
chemical_list: D011743:Pyrimidines; D013141:Spiro Compounds; D061567:Voltage-Gated Sodium Channel Blockers; D061566:Voltage-Gated Sodium Channels; C086364:crambescin B; D014701:Veratridine
keywords: Crambescin B; Tetrodotoxin; Veratridine; Voltage-sensitive sodium channels; Whole-cell patch-clamp recordings