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

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 I-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：I-NBP （0.01-10 pmol/L） showed concentration-dependent inhibition on TREK-1 currents （IC50=0.06＋0.03 pmoVL）, with a maximum current reduction of 70% at a concentration of 10 μmol/L./-NBP showed a more potent inhibition on TREK-1 current than d-NBP or dI-NBP. This effect was partially reversed upon washout and was not voltage-dependent. I-NBP 10 μmoVL elevated the membrane potential in TREK-1/CHO cells from -55.3 mVto -42.9 mV. However, it had no effect on the membrane potential of Wt/CHO cells. Conclusion： I-NBP potently inhibited TREK-1 current and elevated the membrane potential, which may contribute to its neuroprotective activity.