Open AccessInhibitory effects of coronary vasodilator papaverine on heterologously‐expressed HERG currents in Xenopus oocytes
Author(s) -
KIM Cukseong,
LEE Nam,
SON Sookjin,
LEE Kyuseung,
KIM Hyoshin,
KWAK Yonggeun,
CHAE Soowan,
LEE Sangdo,
JEON Byeonghwa,
PARK Jinbong
Publication year - 2007
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2007.00507.x
Subject(s) - herg , papaverine , voltage clamp , xenopus , pharmacology , chemistry , patch clamp , cardiac action potential , ic50 , ventricular action potential , dofetilide , electrophysiology , medicine , membrane potential , endocrinology , biophysics , potassium channel , biology , repolarization , biochemistry , qt interval , in vitro , gene
Aim: To characterize the effects of papaverine on HERG channels expressed in Xenopus oocytes as well as cardiac action potential in rabbit ventricular myocytes. Methods: 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. Results: Papaverine increased the cardiac action potential duration in rabbit ventricular myocytes. It blocked heterologously‐expressed HERG currents in a concentration‐dependent manner (IC 50 71.03±4.75 μmol/L, NH 0.80, n =6), whereas another phosphodiesterase inhibitor, theophylline (500 μmol/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 μS of the control to 56.84±5.33, 36.06±6.53, and 27.09±5.50 μS ( n =4) by 30, 100, and 300 μmol/L of papaverine, respectively. Papaverine (100 μmol/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. Conclusion: 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.