Inhibition of veratridine-induced delayed inactivation of the voltage-sensitive sodium channel by synthetic analogs of crambescin B |
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Authors: | Tadaaki Tsukamoto Yukie Chiba Atsuo Nakazaki Yuki Ishikawa Yoshiki Nakane Yuko Cho Mari Yotsu-Yamashita Toshio Nishikawa Minoru Wakamori Keiichi Konoki |
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Affiliation: | 1. Graduate School of Agricultural Science, Tohoku University, Aoba, Sendai 981-8555, Japan;2. Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan;3. Graduate School of Dentistry, Tohoku University, Aoba, Sendai 980-8575, Japan |
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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 ?100 mV to the test potential of ?10 mV 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. |
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Keywords: | Voltage-sensitive sodium channels Whole-cell patch-clamp recordings Tetrodotoxin Crambescin B Veratridine |
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