Referenced in: none

Automatically associated channels: Kv1.5 , Kv11.1 , Slo1

Title: Electropharmacological properties of telmisartan in blocking hKv1.5 and HERG potassium channels expressed on Xenopus laevis oocytes.

Authors: Dan-Na Tu, Yu-hua Liao, An-Ruo Zou, Yi-Mei Du, Qi Run, Xian-Pei Wang, Lu Li

Journal, date & volume: Acta Pharmacol. Sin., 2008 Aug , 29, 913-22

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/18664324

Abstract
The objectives of this study were to investigate the inhibitory action of telmisartan, a selective angiotensin II type 1 receptor antagonist, on hKv1.5 and human ether-a-go-go-related gene (HERG) channels expressed on Xenopus laevis oocytes.hKv1.5 and HERG channels were expressed on Xenopus laevis oocytes and studied using the 2-microelectrode voltage clamp technique.In hKv1.5 channels, telmisartan produced a voltage- and concentration-dependent inhibition; the efficacies of blockade were different at peak and 1.5 s end-pulse currents, which were 7.75%+/-2.39% (half-maximal inhibition concentration [IC50]=2.25+/-0.97 micromol/L) and 52.64%+/-3.77% (IC50=0.82+/-0.39 micromol/L) at 1 micromol/L telmisartan, respectively. Meanwhile, telmisartan accelerated the inactivation of the channels. However, telmisartan exhibited a low affinity for HERG channels (IC50=24.35+/-5.06 micromol/L); the blockade was voltage- and concentration-dependent. Telmisartan preferentially blocked open-state HERG channels. The slow time constants of deactivation were accelerated (n=6, P<0.05), which was inconsistent with the "foot-in-the-door"effect.Telmisartan blocks hKv1.5 potassium channels involving open and inactivated states at plasma concentration levels of therapeutic doses; whereas the blockade of HERG channels occurs only at supra plasma concentration levels of therapeutic doses and preferentially in open and closed-state channels.