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

Abstract

BackgroundImperatorin 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. MethodsWe investigated the effects of imperatorin on K+ channels using whole-cell configuration voltage-clamp technique. ResultsImperatorin 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 (100μM), imperatorin also suppressed KATP channels. ConclusionOur results suggest that imperatorin inhibited both Kv and KATP channels.