Transient outward current modulates discontinuous conduction in rabbit ventricular cell pairs

Objective: While several studies have demonstrated that the L-type calcium current maintains discontinuous conduction, the contribution of the transient outward current (I-to) to conduction remains unclear. This study evaluated the effects of I-to inhibition on conduction between ventricular myocytes. Methods: An electronic circuit with a variable resistance (R-j) was used to electrically couple single epicardial myocytes isolated from rabbit right ventricle. We inhibited I-to with 4-aminopyridine superfusion, rate-acceleration, or premature stimulation to evaluate the subsequent effects on conduction delay and the critical R-j, which was quantified as the highest R-j that could be imposed before conduction failed. Results: I-to inhibition significantly enhanced conduction in all cell pairs (n = 23). Pharmacologic inhibition of I-to resulted in a 32 +/- 5% decrease in conduction delay and a 36 +/- 7% increase in critical R-j. 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 R-j. Finally, premature action potentials conducted with a 41 +/- 4% shorter conduction delay and a 73 +/- 24% higher critical R-j than basic action potentials. Conclusions: I-to inhibition significantly enhanced conduction across high R-j. These results suggest I-to may contribute to rate-dependent conduction abnormalities. (C) 2001 Elsevier Science B.V. All rights reserved.