title: Novel neuroprotectant chiral 3-n-butylphthalide inhibits tandem-pore-domain potassium channel TREK-1.
abstract: OBJECTIVE
  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 (IC(50)=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.
  
  
  CONCLUSIONS
  1-NBP potently inhibited TREK-1 current and elevated the membrane potential, which may contribute to its neuroprotective activity.
authors.affiliation: Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xin-cai
authors.initials: XC
authors.lastname: Ji
authors.forename: Wan-hong
authors.initials: WH
authors.lastname: Zhao
authors.forename: Dong-xu
authors.initials: DX
authors.lastname: Cao
authors.forename: Qiao-qiao
authors.initials: QQ
authors.lastname: Shi
authors.forename: Xiao-liang
authors.initials: XL
authors.lastname: Wang
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000008:administration & dosage / Q000494:pharmacology*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D008564:Membrane Potentials / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D024683:Potassium Channels, Tandem Pore Domain / Q000037:antagonists & inhibitors*; D051381:Rats; D013237:Stereoisomerism
chemical_list: D001572:Benzofurans; D018696:Neuroprotective Agents; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1; C027125:3-n-butylphthalide