title: Inhibitory effects of coronary vasodilator papaverine on heterologously-expressed HERG currents in Xenopus oocytes.
abstract: OBJECTIVE
  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 (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.
  
  
  CONCLUSIONS
  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.
authors: Department of Physiology, College of Medicine, Chungnam National University, Daejeon 301131, Korea.
authors: Cuk-seong
authors: CS
authors: Kim
authors: Nam
authors: N
authors: Lee
authors: Sook-jin
authors: SJ
authors: Son
authors: Kyu-seung
authors: KS
authors: Lee
authors: Hyo-shin
authors: HS
authors: Kim
authors: Yong-geun
authors: YG
authors: Kwak
authors: Soo-wan
authors: SW
authors: Chae
authors: Sang-do
authors: SD
authors: Lee
authors: Byeong-hwa
authors: BH
authors: Jeon
authors: Jin-bong
authors: JB
authors: Park
mesh_terms: D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D051638:Ether-A-Go-Go Potassium Channels / Q000187:drug effects* / Q000235:genetics*; D008297:Male; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D010208:Papaverine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology*; D014981:Xenopus
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; D026902:Potassium Channel Blockers; D014665:Vasodilator Agents; D010208:Papaverine