Referenced in: none

Automatically associated channels: Kv1.2 , Kv2.1 , TRP

Title: Inhibitory effects of imperatorin on voltage-gated K(+) channels and ATP-sensitive K(+) channels.

Authors: Yu-Wen Wang, Chin-Tsang Yang, Yi-Hung Chen, Chi-Li Gong, Yu-Fang Chen, Yueh-Hsiung Kuo, Yuk-Man Leung

Journal, date & volume: Pharmacol Rep, 2015 Feb , 67, 134-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25560587

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