Affiliation:
1. the Department of Physiology, Loyola University Chicago, Stritch School of Medicine, Maywood, Ill.
Abstract
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 Ca
2+
current (I
Ca,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 μmol/L ACh elicited a rebound stimulation of I
Ca,L
in both SAN (33±4%) and LAP (50±6%) cells above control. Similarly, withdrawal of ACh (1 μmol/L) elicited a rebound stimulation of I
f
in both SAN (21±4%) and LAP (20±6%) cells. During the rebound stimulation of I
Ca,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 μmol/L), an inhibitor of cAMP-dependent protein kinase A, abolished the rebound increase of I
Ca,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 I
Ca,L
. These findings are the first demonstration of an intrinsic cellular mechanism that may contribute directly to the nonadrenergic component of postvagal tachycardia.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine,Physiology
Reference27 articles.
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2. Loeb JM, Vassalle M. Adrenergic mechanisms in postvagal tachycardia. J Pharmacol Exp Ther. 1979;210:56-63.
3. An experimental analysis of the tachycardia that follows vagal stimulation
4. Postvagal tachycardia
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