Referenced in: none

Automatically associated channels: Kv1.2 , Slo1

Title: Dependence of 6beta-acetoxy-7alpha-hydroxyroyleanone block of Kv1.2 channels on C-type inactivation.

Authors: Yuk-Man Leung, Kar-Lok Wong, Chia-Huei Lin, Chia-Chia Chao, Chun-Hsiao Chou, Li-Yun Chang, Siao-Wei Chen, Tzu-Hurng Cheng, Yueh-Hsiung Kuo

Journal, date & volume: Cell. Mol. Life Sci., 2010 Jan , 67, 147-56

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/19865797

Abstract
Voltage-gated K(+) (Kv) channels exhibit slow or C-type inactivation during continuous depolarization. A selective pharmacological agent targeting C-type inactivation is hitherto lacking. Here, we report that 6beta-acetoxy-7alpha-hydroxyroyleanone (AHR), a diterpenoid compound isolated from Taiwania cryptomerioides, can selectively modify C-type inactivation of Kv1.2 channels. Extracellular, but not intracellular, AHR (50 muM) dramatically accelerated the slow decay of Kv currents and left-shifted the steady-state inactivation curve. AHR blocked Kv currents with an IC(50) of 17.7 muM. AHR did not affect the kinetics and voltage-dependence of Kv1.2 channel activation. Channel block by AHR was independent of intracellular K(+) concentration. In addition, effect of AHR was much attenuated in a Kv1.2 V370G mutant defective in C-type inactivation. Therefore, block of Kv1.2 channels by AHR did not appear to involve direct occlusion of the outer pore but depended on C-type inactivation. AHR could thus be a probe targeting Kv channel C-type inactivation gate.