title: Arylnaphthalene lignans from Taiwania cryptomerioides as novel blockers of voltage-gated K+ channels.
abstract: Lignans are natural phytochemicals which exhibit multiple pharmacological effects such as anti-inflammation, antivirus and anti-tumor activities. Whether they have effects on neural tissues and ion channels is still unknown. The effects of several arylnaphathalene lignans purified from Taiwania cryptomerioides on voltage-gated K(+) (Kv) channels in mouse neuroblastoma N2A cells were examined. These lignans included Taiwanin E, helioxanthin (HXT) and diphyllin. All lignans showed inhibitory effects on Kv channels and HXT was the most potent compound (IC(50)=1.7 μM). The mechanism of HXT block was further investigated. Its action was found to be extracellular but not intracellular. HXT accelerated current decay, caused a left-shift in steady-state inactivation curve but had no effect on voltage-dependence of activation. HXT block was unaffected by intracellular K(+) concentrations. Further, it did not affect ATP-sensitive K(+) channels. Our data therefore suggest that HXT is a potent and specific blocker of Kv channels, possibly with an inhibitory mechanism involving acceleration of slow inactivation.
authors.affiliation: Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung, Taiwan. ymleung@mail.cmu.edu.tw
authors.forename: Yuk-Man
authors.initials: YM
authors.lastname: Leung
authors.forename: Yi-Huan
authors.initials: YH
authors.lastname: Tsou
authors.forename: Chang-Shin
authors.initials: CS
authors.lastname: Kuo
authors.forename: Shang-Ying
authors.initials: SY
authors.lastname: Lin
authors.forename: Pau-Yen
authors.initials: PY
authors.lastname: Wu
authors.forename: Mann-Jen
authors.initials: MJ
authors.lastname: Hour
authors.forename: Yueh-Hsiung
authors.initials: YH
authors.lastname: Kuo
mesh_terms: D000818:Animals; D052117:Benzodioxoles; D045744:Cell Line, Tumor; D029779:Cupressaceae / Q000737:chemistry*; D004148:Dioxolanes / Q000302:isolation & purification / Q000494:pharmacology; D017705:Lignans / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D052117:Benzodioxoles; D004148:Dioxolanes; D017705:Lignans; D010936:Plant Extracts; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; C505802:helioxanthin; C010130:diphyllin