© 2001 by European Society of Cardiology
Copyright © 2001, European Society of Cardiology
Transient outward current modulates discontinuous conduction in rabbit ventricular cell pairs
aCardiac Rhythm Management Lab and Department of Biomedical Engineering, University of Alabama–Birmingham, Volker Hall B140, 1670 University Blvd., Birmingham, AL 35294, USA
bNora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
* Corresponding author. Tel.: +1-205-975-4718; fax: +1-205-975-4720 djh{at}crml.uab.edu
Objective: While several studies have demonstrated that the L-type calcium current maintains discontinuous conduction, the contribution of the transient outward current (Ito) to conduction remains unclear. This study evaluated the effects of Ito inhibition on conduction between ventricular myocytes. Methods: An electronic circuit with a variable resistance (Rj) was used to electrically couple single epicardial myocytes isolated from rabbit right ventricle. We inhibited Ito with 4-aminopyridine superfusion, rate–acceleration, or premature stimulation to evaluate the subsequent effects on conduction delay and the critical Rj, which was quantified as the highest Rj that could be imposed before conduction failed. Results: Ito inhibition significantly enhanced conduction in all cell pairs (n = 23). Pharmacologic inhibition of Ito resulted in a 32±5% decrease in conduction delay and a 36±7% increase in critical Rj. Similarly, reduction of the basic cycle length from 2 to 0.5 s resulted in a 31±3% decrease in conduction delay and a 31±3% increase in critical Rj. Finally, premature action potentials conducted with a 41±4% shorter conduction delay and a 73±24% higher critical Rj than basic action potentials. Conclusions: Ito inhibition significantly enhanced conduction across high Rj. These results suggest Ito may contribute to rate-dependent conduction abnormalities.
KEYWORDS Arrhythmia (mechanisms); Cell communication; Conduction (block); Ion channels; K-channels; Membrane potential; Ventricular arrhythmias
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