Inhibitory effects of imperatorin on voltage-gated K+ channels and ATP-sensitive K+ channels

Background imperatorin is a furocoumarin isolated from angelica archangelica and cnidium monnieri. it has multiple neuromodulatory actions such as anticonvulsant effects,anxiolytic effects and anti-nociceptive effects. although there have been reports demonstrating its effects on voltage-gated na+ channels (vgsc) and transient reversal potential (trp) v1 channels in neurons,there is hitherto no work showing whether this compound affects voltage-gated k+ (kv) channels and atp-sensitive k+ (katp) channels. methods we investigated the effects of imperatorin on k+ channels using whole-cell configuration voltage-clamp technique. results imperatorin inhibited kv channels in differentiated neuronal ng108-15 cells,and caused a left shift in the steady-state inactivation curve without affecting activation gating. imperatorin also inhibited heterologously expressed wild type kv1.2 and kv2.1 channels,but became much less potent in inhibiting kv1.2 v370g,a mutant defective in c-type inactivation,implying that drug inhibition depends on c-type inactivation. at a high concentration (100 μm),imperatorin also suppressed katp channels. conclusion our results suggest that imperatorin inhibited both kv and katp channels. © 2014 institute of pharmacology,polish academy of sciences. published by elsevier urban and partner sp.z o.o. all rights reserved.