A cellular mechanism contributing to postvagal tachycardia studied in isolated pacemaker cells from cat right atrium

Vagal nerve-induced inhibition of the heartbeat is followed by a postvagal increase in heart rate above control levels, postvagal tachycardia. In the present study, we used a perforated-patch/whole-cell recording method to determine the role of L-type Ca2+ current (ICa,L) and the hyperpolarization-activated inward current (I(f)) in the positive chronotropic response elicited by withdrawal of acetylcholine (ACh). Experiments were performed on sinoatrial node (SAN) and latent atrial pacemaker (LAP) cells isolated from cat right atrium. Withdrawal of a 2-minute exposure to 1 mumol/L ACh elicited a rebound stimulation of ICa,L in both SAN (33 +/- 4%) and LAP (50 +/- 6%) cells above control. Similarly, withdrawal of ACh (1 mumol/L) elicited a rebound stimulation of I(f) in both SAN (21 +/- 4%) and LAP (20 +/- 6%) cells. During the rebound stimulation of ICa,L, peak amplitude was increased throughout the voltage range, and the voltage dependence of activation was shifted to more negative voltages. Action potential recordings from both SAN and LAP cells showed that following ACh-induced inhibition, withdrawal of ACh elicited a concomitant rebound increase in action potential amplitude ( + 21 +/- 2% and + 21 +/- 3%, respectively) and decrease in pacemaker cycle length (30 +/- 5% and 44 +/- 5%, respectively) compared with control. H-89 (2 mumol/L), an inhibitor of cAMP-dependent protein kinase A, abolished the rebound increase of ICa,L, I(f), action potential amplitude, and decrease in pacemaker cycle length elicited by withdrawal of ACh. In the presence of 2 mmol/L cesium, a blocker of I(f), the rebound decrease in pacemaker cycle length elicited by withdrawal of ACh was unchanged. We conclude that in SAN and LAP cells, withdrawal of ACh elicits a positive chronotropic response primarily through a cAMP-mediated rebound stimulation of ICa,L. These findings are the first demonstration of an intrinsic cellular mechanism that may contribute directly to the nonadrenergic component of postvagal tachycardia.