Effects of quinidine on repolarization in canine epicardium, midmyocardium, and endocardium: I. In vitro study.
BACKGROUND
The antiarrhythmic action of quinidine is associated with a slowing of conduction and prolongation of repolarization. The latter effect has no consistent correlation with quinidine actions on action potential duration (APD) in isolated tissue experiments. To enhance our understanding of the mechanisms of quinidine action, we studied its effect on APD in canine epicardial, midmyocardial, and endocardial tissues.


RESULTS
Standard microelectrode techniques were used to study the effects of quinidine 2.5 to 20 micromol/L on APD in ventricular epicardial, endocardial, and transmural (M-cell) slabs at cycle lengths (CLs) from 300 to 4000 ms. Qualitatively different time courses of actions and concentration- and rate-dependent effects were seen in M cells compared with the others. In endocardium and epicardium, quinidine induced monotonic and concentration-dependent APD prolongation at all CLs. In contrast, the effects of quinidine in M cells varied from prolongation to shortening, depending on duration of superfusion, concentration, and CL. Experiments with E4031 and TTX suggested that in M cells, quinidine-induced APD lengthening was attributable to block of delayed rectifier potassium current and APD shortening was due to inhibition of TTX-sensitive steady-state sodium current.


CONCLUSIONS
In vitro, there is a significant difference of quinidine effects in M cells versus epicardial and endocardial cells that appears to reflect differences in the contributions of specific ion channels to the APD at the three sites. The differences may influence the actions of quinidine on repolarization of the heart in situ and determine both the proarrhythmic and antiarrhythmic actions of the drug.
Sosunov
E A
EA
Department of Pharmacology and Pediatrics, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
Anyukhovsky
E P
EP
Rosen
M R
MR
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D004699:Endocardium / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008839:Microelectrodes; D010496:Pericardium / Q000187:drug effects*; D011802:Quinidine / Q000494:pharmacology*; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D007473:Ion Channels; D011802:Quinidine