Referenced in: none

Automatically associated channels: Kv11.1 , Slo1

Title: Inhibitory effects of coronary vasodilator papaverine on heterologously-expressed HERG currents in Xenopus oocytes.

Authors: Cuk-seong Kim, Nam Lee, Sook-jin Son, Kyu-seung Lee, Hyo-shin Kim, Yong-Geun Kwak, Soo-Wan Chae, Sang-do Lee, Byeong-hwa Jeon, Jin-bong Park

Journal, date & volume: Acta Pharmacol. Sin., 2007 Apr , 28, 503-10

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/17376289

Abstract
To characterize the effects of papaverine on HERG channels expressed in Xenopus oocytes as well as cardiac action potential in rabbit ventricular myocytes.Conventional microelectrodes were used to record action potential in rabbit ventricular myocytes. HERG currents were recorded by 2-electrode voltage clamp technique in Xenopus oocytes injected with HERG cRNA.Papaverine increased the cardiac action potential duration in rabbit ventricular myocytes. It blocked heterologously-expressed HERG currents in a concentration-dependent manner (IC50 71.03+/-4.75 micromol/L, NH 0.80, n=6), whereas another phosphodiesterase inhibitor, theophylline (500 micromol/L), did not. The blockade of papaverine on HERG currents was not voltage-dependent. The slope conductance measured as a slope of the fully activated HERG current-voltage curves decreased from 78.03+/-4.25 muS of the control to 56.84+/-5.33, 36.06+/-6.53, and 27.09+/-5.50 microS (n=4) by 30, 100, and 300 micromol/L of papaverine, respectively. Papaverine (100 micromol/L) caused a 9 mV hyperpolarizing shift in the voltage-dependence of steady-state inactivation, but there were no changes in the voltage-dependence of HERG current activation. Papaverine blocked HERG channels in the closed, open, and inactivated states.These results showed that papaverine blocked HERG channels in a voltage- and state-independent manner, which may most likely be the major mechanism of papaverine-induced cardiac arrhythmia reported in humans.