Repolarization differences between guinea pig atrial endocardium and epicardium: evidence for a role of Ito

It has long been known that ventricular epicardial action potential duration (APD) is shorter than endocardial, and recent evidence suggests that a larger transient outward current (Ito) in epicardium is responsible for the difference. To evaluate possible corresponding regional variations in atrial tissue, we studied guinea pig atrial epicardial and endocardial action potentials using standard microelectrode techniques. Epicardial APD was consistently shorter than endocardial, but the difference was greatly diminished by rapid pacing or early premature activation, situations in which Ito availability should be limited. 4-Aminopyridine (4-AP), at concentrations (0.5 mM) producing specific Ito blockade, increased APD significantly in atrial epicardium without affecting endocardium. The effect of 4-AP on APD was most marked at slow rates, at which Ito would be greatest, and was negligible at rapid rates or during premature activation, during which Ito would be largely inactivated. At larger concentrations (5 mM) 4-AP caused an equalization of epicardial and endocardial APD. The equimolar substitution of strontium for calcium did not affect APD at slow rates and increased APD (particularly in endocardium) at rapid rates, suggesting that the Ito underlying endocardial-epicardial differences was unlikely to be calcium dependent. We conclude that epicardial-endocardial differences in APD, well documented in ventricular tissue, can also occur in atrial tissue and that the underlying ionic mechanisms appear to be similar.