Quinidine-induced open channel block of K+ current in rat ventricle.
1. The effects of quinidine on calcium-independent outward K+ currents in rat ventricular myocytes were studied using whole-cell patch clamp techniques. 2. Quinidine sulphate (6 microM) significantly prolonged repolarization of the ventricular action potential. This effect was larger during early repolarization (25% level) than at later times (90% level). 3. Quinidine reduced the amplitude of a transient outward current, and accelerated its rate of decay by approximately 4 fold at membrane potentials between 0 to +50 mV. Quinidine also reduced the amplitude of a slowly inactivating, tetraethylammonium-sensitive 'pedestal' component of the outward current. 4. The quinidine-induced block of the transient outward current was dependent on time and membrane potential. Maximal block occurred with depolarizations of about 100 ms duration, and longer depolarizations (up to 1.5 s) produced little additional block. The membrane potential dependence of quinidine-induced block was very similar to the membrane potential dependence of activation of the transient outward current. The membrane potential dependence of steady-state inactivation of the transient outward current was not significantly affected by quinidine. 5. These results show that quinidine blocks outward K+ currents in rat ventricular cells. The time and potential dependence of this block suggests that quinidine blocks the transient outward K+ current by acting primarily on the open state of these channels.
Clark
R B
RB
Department of Medical Physiology, University of Calgary, School of Medicine, Alberta, Canada.
Sanchez-Chapula
J
J
Salinas-Stefanon
E
E
Duff
H J
HJ
Giles
W R
WR
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004594:Electrophysiology; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects; D011802:Quinidine / Q000494:pharmacology*; D051381:Rats; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D011802:Quinidine