Electrophysiological responses of canine atrial endocardium and epicardium to acetylcholine and 4-aminopyridine

OBJECTIVES: Prior studies demonstrated marked electrophysiological and pharmacological differences between canine ventricular epicardium and endocardium. For atrium, however, it has been assumed that, because of the thin wall, electrical properties of epicardium and endocardium are similar. The aim of the present study was to compare the action potential (AP) characteristics in epicardial and endocardial atrial cells before and following addition of acetylcholine (ACh) and 4-aminopyridine (4-AP). METHODS AND RESULTS: Microelectrode techniques were used to study the effects of ACh (10(-7)-10(-5) M) and 4-AP (0.5 mM) on epicardial and endocardial AP of canine right atrial free wall at cycle lengths (CL) of 250 to 2000 ms. ACh hyperpolarized epicardial and endocardial cells (by 5-8 mV at 10(-5) M). In control, AP duration to 90% repolarization (APD90) was longer in endocardium at all CL. ACh shortened APD90 in either tissue with more prominent effect in endocardium (at 10(-5) M and CL = 2000 ms, from 179 +/- 10 to 90 +/- 11 ms in epicardium and from 209 +/- 10 to 65 +/- 6 ms in endocardium, P < 0.05). As a result, at 10(-5) M, APD90 in endocardium was shorter than in epicardium at all CL 4-AP effects on AP duration were similar in both tissue types. No effects of 4-AP was seen at CL = 250 ms and at long CL, the compound shortened APD90 and prolonged AP duration to 50% repolarization. CONCLUSIONS: (1) ACh exerts direct effects on atrial epicardial and endocardial AP; (2) 4-AP-sensitive transient outward current (Itol) is expressed both in canine atrial epicardial and endocardial cells; (3) differential response of epicardial and endocardial APD to ACh may alter the gradient of repolarization across the atrial wall and contribute to vagally induced atrial flutter and fibrillation.