title: Selective blocking effects of 4,9-anhydrotetrodotoxin, purified from a crude mixture of tetrodotoxin analogues, on NaV1.6 channels and its chemical aspects.
abstract: Tetrodotoxin (TTX) is a potent neurotoxin found in a number of marine creatures including the pufferfish, where it is synthesized by bacteria and accumulated through the food chain. It is a potent and selective blocker of some types of voltage-gated Na+ channel (NaV channel). 4,9-Anhydrotetrodotoxin (4,9-anhydroTTX) was purified from a crude mixture of TTX analogues (such as TTX, 4-epiTTX, 6-epiTTX, 11-oxoTTX and 11-deoxyTTX) by the use of liquid chromatography-fluorescence detection (LC-FLD) techniques. Recently, it has been reported that 4,9-anhydroTTX selectively blocks the activity of NaV1.6 channels with a blocking efficacy 40-160 times higher than that for other TTX-sensitive NaV1.x channel isoforms. However, little attention has been paid to the molecular properties of the α-subunit in NaV1.6 channels and the characteristics of binding of 4,9-anhydroTTX. From a functional point of view, it is important to determine the relative expression of NaV1.6 channels in a wide variety of tissues. The aim of this review is to discuss briefly current knowledge about the pharmacology of 4,9-anhydroTTX, and provide an analysis of the molecular structure of native NaV1.6 channels. In addition, chemical aspects of 4,9-anhydroTTX are briefly covered.
authors: Department of Pharmacology, Faculty of Medicine, Saga University, Saga 849-8501, Japan. noritera@cc.saga-u.ac.jp.|Laboratory of Biomedical Engineering, Graduate School of Biomedical Engineering, Tohoku University, Sendai 980-8575, Japan. noritera@cc.saga-u.ac.jp.
authors: Noriyoshi
authors: N
authors: Teramoto
authors: Laboratory of Bioorganic Chemistry of Natural Products, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan. myama@biochem.tohoku.ac.jp.
authors: Mari
authors: M
authors: Yotsu-Yamashita
mesh_terms: D000818:Animals; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D062557:NAV1.6 Voltage-Gated Sodium Channel / Q000187:drug effects* / Q000235:genetics; D026941:Sodium Channel Blockers / Q000138:chemical synthesis / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D062557:NAV1.6 Voltage-Gated Sodium Channel; C491046:Scn8a protein, mouse; D026941:Sodium Channel Blockers; C047739:anhydrotetrodotoxin; D013779:Tetrodotoxin