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.
Cardiac Rhythm Management Lab and Department of Biomedical Engineering, University of Alabama-Birmingham, Volker Hall B140, 1670 University Blvd., Birmingham, AL 35294, USA. djh@crml.uab.edu
D J
DJ
Huelsing
A E
AE
Pollard
K W
KW
Spitzer
D015761:4-Aminopyridine / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism*; D002450:Cell Communication; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D004558:Electric Stimulation; D006352:Heart Ventricles / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects*; D011817:Rabbits
D015221:Potassium Channels; D015761:4-Aminopyridine