Arylnaphthalene lignans from Taiwania cryptomerioides as novel blockers of voltage-gated K+ channels.
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.
Leung
Yuk-Man
YM
Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung, Taiwan. ymleung@mail.cmu.edu.tw
Tsou
Yi-Huan
YH
Kuo
Chang-Shin
CS
Lin
Shang-Ying
SY
Wu
Pau-Yen
PY
Hour
Mann-Jen
MJ
Kuo
Yueh-Hsiung
YH
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
D052117:Benzodioxoles; D004148:Dioxolanes; D017705:Lignans; D010936:Plant Extracts; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; C505802:helioxanthin; C010130:diphyllin