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Novel neuroprotectant chiral 3-n-butylphthalide inhibits tandem-pore-domain potassium channel TREK-1

  
@article{APS5802,
	author = {Xin-cai Ji and Wan-hong Zhao and Dong-xu Cao and Qiao-qiao Shi and Xiao-liang Wang},
	title = {Novel neuroprotectant chiral 3-n-butylphthalide inhibits tandem-pore-domain potassium channel TREK-1},
	journal = {Acta Pharmacologica Sinica},
	volume = {32},
	number = {2},
	year = {2016},
	keywords = {},
	abstract = {Aim: To study the effects of 3-n-butylphthalide (NBP) on the TREK-1 channel expressed in Chinese hamster ovary (CHO) cells.
Methods: Whole-cell patch-clamp recording was used to record TREK-1 channel currents. The effects of varying doses of l-NBP on TREK-1 currents were also observed. Current-clamp recordings were performed to measure the resting membrane potential in TREK-1-transfected CHO (TREK-1/CHO) and wild-type CHO (Wt/CHO) cells.
Results: l-NBP (0.01–10 μmol/L) showed concentration-dependent inhibition on TREK-1 currents (IC50=0.06±0.03 μmol/L), with a maximum current reduction of 70% at a concentration of 10 μmol/L. l-NBP showed a more potent inhibition on TREK-1 current than d-NBP or dl-NBP. This effect was partially reversed upon washout and was not voltage-dependent. l-NBP 10 μmol/L elevated the membrane potential in TREK-1/CHO cells from -55.3 mV to -42.9 mV. However, it had no effect on the membrane potential of Wt/CHO cells.
Conclusion: l-NBP potently inhibited TREK-1 current and elevated the membrane potential, which may contribute to its neuroprotective activity.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/5802}
}