Effects of diltiazem and nifedipine on transient outward and ultra-rapid delayed rectifier potassium currents in human atrial myocytes.
1. It is unknown whether the widely used L-type Ca(2+) channel antagonists diltiazem and nifedipine would block the repolarization K(+) currents, transient outward current (I(to1)) and ultra-rapid delayed rectifier K(+) current (I(Kur)), in human atrium. The present study was to determine the effects of diltiazem and nifedipine on I(to1) and I(Kur) in human atrial myocytes with whole-cell patch-clamp technique. 2. It was found that diltiazem substantially inhibited I(to1) in a concentration-dependent manner, with an IC(50) of 29.2+/-2.4 microM, and nifedipine showed a similar effect (IC(50)=26.8+/-2.1 muM). The two drugs had no effect on voltage-dependent kinetics of the current; however, they accelerated I(to1) inactivation significantly, suggesting an open channel block. 3. In addition, diltiazem and nifedipine suppressed I(Kur) in a concentration-dependent manner (at +50 mV, IC(50)=11.2+/-0.9 and 8.2+/-0.8 microM, respectively). These results indicate that the Ca(2+) channel blockers diltiazem and nifedipine substantially inhibit I(to1) and I(Kur) in human atrial myocytes.
Gao
Zhan
Z
Department of Medicine and Research Centre of Heart, Brain, Hormone and Health Aging, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Sun
Haiying
H
Chiu
Shui-Wah
SW
Lau
Chu-Pak
CP
Li
Gui-Rong
GR
D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002478:Cells, Cultured; D051668:Delayed Rectifier Potassium Channels; D004110:Diltiazem / Q000494:pharmacology*; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D024683:Potassium Channels, Tandem Pore Domain / Q000037:antagonists & inhibitors*; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors*
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D051668:Delayed Rectifier Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D024642:Potassium Channels, Voltage-Gated; D004110:Diltiazem; D009543:Nifedipine